Polymeric blends with zwitterionic groups

ABSTRACT

Disclosed is a polymer blend composition and shaped article, and a process of blending and making shaped articles of polymer blends in which the biocompatibility of various polymers is improved by blending with them a polymer including a zwitterionic group. The zwitterionic group is usually an ammonium phosphate ester, preferably a choline, zwitterionic group and the polymer containing it may be produced by the free radical polymerization of ethylenically unsaturated monomers including a monomer bearing the zwitterionic group. Blending of the two polymers may be achieved by dry blending particulate polymers or by mixing the polymers in liquid dispersion or solution followed by removal of the liquid medium. The fibrinogen absorption and/or platelet activation of polymers may be reduced to a value of less than 80% or even less than 60% of the base polymer by introducing amounts of more than 10% or more than 30% of the zwitterionic group containing polymer.

This is a divisional of Application Ser. No. 08/290,901 filed Dec. 5,1994 now U.S. Pat. No. 5,712,326, which was the National Stage ofInternational Application PCT/GB93/02652, filed Dec. 23, 1993.

The present invention relates to new polymeric materials, especiallysuitable for use in biomedical applications, processes for theirproduction, articles formed from such materials and processes formodifying the physical and biological properties of plastic materials.

The medical device industry frequently employs a range of thermoplastic,elastomeric and thermoset materials in medical devices. Many of thesepolymers were originally developed as engineering materials and theirphysical and mechanical properties reflect this. Thus a plastic may beemployed as a medical device because it posseses physical and mechanicalproperties suitable for use in a biological environment. However, untilrecently little attention was paid to the biological properties of thesematerials. This has resulted in a number of problems with current devicematerials as a result of adverse biological reactions. Silicone rubbershave been shown to leach toxic silicones when implanted, polyurethaneshave been found to degrade by macrophage attack and natural rubbers havecaused severe allergic reactions. In addition, PVC, a widely usedpolymer for medical devices, often contains large quantities of theplasticiser bis-(2-ethylhexyl)phthalate and many studies now show thisto be toxic. It is clear, therefore, that many materials possessproperties which render them unsuitable for use in biologicalapplications.

Previous-attempts to prepare biocompatible materials have mimicked thesurface of platelet cells which under normal circumstances exist in theblood without causing any adverse reactions. These cell membranescomprise a phospholipid bilayer with the phosphorylcholine groupdominating the external membrane surface. It is believed this outersurface avoids adverse reaction with other biological components. Lipidscontaining phosphorylcholine groups have been coated on to the surfaceof device materials and bloodclotting studies showed that they renderedthe surface more biocompatible (J A Hayward & D Chapman, Biomaterials,Vol. 5, 135, 1984). These phospholipids have also been used asplasticisers in commercial polymers and have again improved thebiocompatibility of the base material (WO-A-87/02684). However these twoapproaches nevertheless possess disadvantages.

Coating the surface of a finished device has a number of problems, onebeing the difficulty in coating devices with complex shapes or multiplecomponents; in practice a multi-component device can be impossible tocoat. In addition the degree of biocompatibility is dependent on thequality of the coating and how strongly it is bound to the surface; thusdefects or scratches in the coating will reduce its effectiveness. Theuse of a lipid as a plasticiser goes some way to overcome theseproblems, but the lipid is free to move through the material and caneventually leach out of the system. This can again lead to a reductionin the level of biocompatibility. The lipid also has in addition nomechanical strength and can therefore only be used to soften the basepolymer.

We have now devised new blended polymeric materials which seek toovercome these disadvantages. The blends combine the desirable physicaland/or mechanical properties of an engineering polymer with thebiocompatible properties of a polymer bearing pendant zwitterionic, forexample phosphoryl choline, groups.

The present invention accordingly provides a polymer blend comprising:

(A) a polymer bearing zwitterionic pendant groups; and

(B) a polymer having desirable mechanical and/or physical properties.

The extent to which a polymer bearing zwitterionic pendant groups (A)renders a further polymer biocompatible in a blend may be assessed as acombination of factors such as reduction in the extent to which theblend causes blood platelet activation and protein adsorption, (forinstance as judged by absorption of fibrinogen from human plasma).

(A) Polymer bearing zwitterionic pendant groups

The polymer bearing zwitterionic pendant groups may be either ahomopolymer or a copolymer. Preferably it is a polymer of residues ofone or more radically polymerisable monomers, more preferablyethylenically unsaturated monomers. Preferably the polymer bearszwitterionic pendant groups by virtue of one of the starting monomersfrom which it is produced carrying such a group. Instead thezwitterionic group may be introduced onto a preformed polymer, forinstance by reactions such as are disclosed in EP-A-0157469,WO-A-9113639, WO-A-9207858 or WO-A-9305081. The polymer may be acondensation polymer, for instance a polyurethane or a polyester. Againthe zwitterionic group is present on the polymer either by incorporationas a pendant group on one of the starting monomers or by post-reactionof a preformed polymer. Polyurethanes are described in WO-A-8602933 andWO-A-89305081 and polyesters and described in WO-8800956.

Preferably the zwitterionic group is a group X as defined below.

Preferably the polymer is a copolymer of a comonomer containing azwitterionic group and a comonomer containing an alkyl, usually ahydrophobic group, a reactive functional group, or an ionic group. Thepresence of residues of such comonomers may serve to improve thecompatability of the polymer (A) for the polymer (B) in the blend of thepresent invention. Copolymers containing residues of a comonomer whichcontain a hydrophobic group are particularly preferred.

As examples of comonomers containing as hydrophobic groups, mention maybe made of comonomers containing as pendant groups alkyl groups orfluoroalkyl groups, optionally having one or more etheric oxygen atomsinterrupting the carbon chain, and optionally containing one or morecarbon-carbon double or triple ones. Alternatively such comonomers maycontain as pendant groups siloxane groups, preferably containing from 1to 50, more preferably 5 to 30, silicon atoms.

The nature of such hydrophobic groups may be chosen for compatabilitywith polymer (B). For example comonomers containing a hydrophobicfluoroalkyl group are particularly suitable for blending withfluoropolymer such as polyvinylidene fluoride (PVDF).

Alternatively, the polymer may comprise residues of a monomer containingboth a zwitterionic group and such a hydrophobic group.

Preferably, such a hydrophobic group is an alkyl or fluoroalkyl group,optionally containing one or more carbon-carbon double or triple bonds.More preferably, the hydrophobic group does not contain any ethylenicunsaturation.

Alternatively, or in addition, such copolymers may further compriseresidues of a comonomer containing a reactive functional group or anionic group. Such reactive groups may serve to crosslink the copolymer(A) and/or bind the copolymer (A) to the polymer (B) having desirablephysical and/or mechanical properties. In addition such reactive groupsmay provide reactive moieties at the surface of the blend. Use of acomonomer of containing ionic groups may serve to improve themiscability of the polymer (A) with polymer (B) where polymer (B) itselfbears ionically charged groups.

In addition, the polymer (A) may further comprise residues of one ormore diluent comonomers.

Monomers and comonomers of ethylenically unsaturated monomers which maybe used in the preferred polymers (A) will now be described in moredetail.

It is to be understood that throughout the specification (alk)acrylate,(alk)acrylic and (alk)acrylamide mean acrylate or alkacrylate, acrylicor alkacrylic and acrylamide or alkacrylamide respectively. Preferablyunless otherwise stated alkacrylate, alkacrylic and alkacrylamide groupscontain from 1 to 4 carbon atoms in the alkyl group thereof and are mostpreferably methacrylate, methacrylic or methacrylamide groups. Similarly(meth)acrylate, (meth)acrylic and (meth)acrylamide shall be understoodto mean acrylate or methacrylate, acrylic or methacrylic and acrylamideor methacrylamide respectively.

A.1. Monomers Containing a Zwitterionic Group

Preferred comonomers which contain a zwitterionic group are of generalformula (I)

    Y--B--X                                                    (I)

wherein B is a straight or branched alkylene, oxaalkylene oroligo-oxaalkylene chain optionally containing one or more fluorine atomsup to and including perfluorinated chains or, if X contains acarbon-carbon chain between B and the zwitterionic moiety or if Ycontains a terminal carbon atom bonded to B, a valence bond;

X is a zwitterionic group and

Y is an ethylenically unsaturated polymerisable group selected from##STR1## wherein: R is hydrogen or a C₁ -C₄ alkyl group;

A is --O-- or --NR¹ -- where R¹ is hydrogen or a C₁ -C₄ alkyl group orR¹ is --B--X where B and X are as defined above; and

K is a group --(CH₂)_(p) OC(O)--, --(CH₂)_(p) C(O)O--, --(CH₂)_(p)OC(O)O--, --(CH₂)_(p) NR² --, --(CH₂)_(p) NR² C(O)--, --(CH₂)_(p)C(O)NR² --, --(CH₂)_(p) NR² C(O)O--, --(CH₂)_(p) OC(O)NR² --,--(CH₂)_(p) NR² C(O)NR² --, (in which the groups R² are the same ordifferent) --(CH₂)_(p) O--, --(CH₂)_(p) SO₃ --, or, optionally incombination with B, a valence bond and p is from 1 to 12 and R² ishydrogen or a C₁ -C₄ alkyl group.

The proviso on whether B may be a valence bond ensures that thezwitterionic moiety in X is not directly bonded to a heteroatom, such asan oxygen or nitrogen atom in Y.

Preferred monomers containing a zwitterionic group are therefore ofgeneral formula (II) or (III). ##STR2## where R, A, B, K and X are asdefined with reference to formula (I).

Preferably in the compounds of formula (II) R is hydrogen, methyl, orethyl, more preferably methyl, so that (II) is an acrylic acid,methacrylic acid or ethacrylic acid derivative.

In the compounds of formula (III) K may be a valence bond and B a group,K may be a group and B a valence bond, both K and B may be groups, or Kand B may together be a valence bond. Preferably B is a group where K isa valence bond.

Where K is a group then preferably p is from 1 to 6, more preferably 1,2or 3 and most preferably p is 1. When K is a group --(CH₂)_(p) NR² --,--(CH₂)_(p) NR² C(O)--, --(CH₂)_(p) C(O)NR², --(CH₂)_(p) NR² C(O)O--,--(CH₂)_(p) OC(O)NR² -- or --(CH₂)_(p) NR² C(O)NR² -- then R² ispreferably hydrogen, methyl or ethyl, more preferably hydrogen.

In the compounds of formula (III) preferably the vinyl group is para tothe group --K--B--X.

Preferably B is:

an alkylene group of formula --(CR³ ₂)_(a) --, wherein the groups --(CR³₂)-- are the same or different, and in each group --(CR³ ₂)-- the groupsR³ are the same or different and each group R³ is hydrogen, fluorine orC₁₋₄ alkyl or fluoroalkyl, preferably hydrogen, and a is from 1 to 12,preferably 1 to 6;

an oxaalkylene group such as alkoxyalkyl having 1 to 6 carbon atoms ineach alkyl moiety, more preferably --CH₂ O (CH₂)₄ --; or

an oligo-oxaalkylene group of formula --[(CR⁴ ₂)_(b) O]_(c) (CR⁴ ₂)_(b)-- where the groups --(CR⁴ ₂)-- are the same or different and in eachgroup --(CR⁴ ₂)-- the groups R⁴ are the same or different and each groupR⁴ is hydrogen, fluorine or C₁₋₄ alkyl or fluoroalkyl, preferablyhydrogen, and b is from 1 to 6, preferably 2 or 3 and c is from 2 to 11,preferably 2 to 5; or

if X contains a carbon-carbon chain between B and the centre ofpermanent positive charge or if Y contains a terminal carbon atom, avalence bond.

Preferred groups B include alkylene, oxaalkylene and oligo-oxaalkylenegroups of up to 12 carbon atoms optionally containing one or morefluorine atoms.

In compounds of formula (III) it is preferred that K and B contain up to12 carbon atoms in total.

Preferred zwitterionic groups for instance which are groups onethylenically unsaturated monomer YBX are groups in which the cationicmoiety is based on a quaternary ammonium group and the anionic moiety isbased on a phosphate group. Preferred zwitterionic groups are ammoniumphosphate ester zwitterionic groups. Usually the cationic is located atthe end of pendant group X distant from B. Most preferred are the groupsof formula (IVA), (IVB), (IVC), (IVD) and (IVE) as defined below:monomers containing such groups may be used alone in homopolymers or incombination with further comonomers to provide a copolymer. Of thesegroups (IVB) are particularly preferred.

In addition, groups of formula (VA), (VB) and (VC) are preferred asmonomers containing both a zwitterionic group and a hydrophobic alkyl,fluoroalkyl or siloxane group.

The groups of formula (IVA) are: ##STR3## where the groups R⁶ are thesame or different and each is hydrogen or C₁₋₄ alkyl and d is from 2 to4.

Preferably the groups R⁶ are the same. It is also preferable that atleast one of the groups R⁶ is methyl, and more preferable that thegroups R⁶ are both methyl.

Preferably d is 2 or 3, more preferably 3.

When X is a group of formula (IVA) preferably B is a group of formula--(CR³ ₂)-- or --(CR³ ₂)₂ --, eg. --(CH₂)-- or --(CH₂ CH₂)--.

The groups of formula (IVB) are: ##STR4## where the groups R⁷ are thesame or different and each is hydrogen or C₁₋₄ alkyl, and e is from 1 to4.

Preferably the groups R⁷ are the same. It is also preferable that atleast one of the groups R⁷ is methyl, and more preferable that thegroups R⁷ are all methyl.

Preferably e is 2 or 3, more preferably 2.

When X is a group of formula (IVB) preferably B is a group of formula--(CR³ ₂)-- or --(CR³ ₂)₂ --, eg. --(CH₂)-- or --(CH₂ CH₂)--.

The groups of formula (IVC) are: ##STR5## wherein the groups R⁸ are thesame or different and each is hydrogen or C₁₋₄ alkyl, R^(8a) is hydrogenor, more preferably, a group --C(O)B¹ R^(8b) where R^(8b) is hydrogen ormethyl, preferably methyl, B¹ is a valence bond or straight or branchedalkylene, oxaalkylene or oligo-oxaalkalyene group, and f is from 1 to 4;and

if B is other than a valence bond z is 1 and if B is a valence bond z isO, if X is directly bonded to an oxygen or nitrogen atom and otherwise zis 1.

Preferably the groups R⁸ are the same. It is also preferable that atleast one of the groups R⁸ is methyl, and more preferable that thegroups R⁸ are all methyl.

Preferably f is 1 or 2, more preferably 2.

Preferably B¹ is:

a valence bond;

an alkylene group of formula --(CR^(3a) ₂)_(aa) --, wherein the groups--(CR^(3a) ₂)-- are the same or different, and in each group --(CR^(3a)₂)-- the groups R^(3a) are the same or different and each group R^(3a)is hydrogen or C₁₋₄ alkyl, preferably hydrogen, and aa is from 1 to 12,preferably 1 to 6;

an oxaalkylene group such as alkoxyalkyl having 1 to 6 carbon atoms ineach alkyl moiety, more preferably --CH₂ O(CH₂)₄ --; or

an oligo-oxaalkylene group of formula --[(CR^(4a) ₂)_(ba) O]_(ca) --where the groups --(CR_(4a) ₂)-- are the same or different and in eachgroup --(CR^(4a) ₂) the groups R^(4a) are the same or different and eachgroup R^(4a) is hydrogen or C₁₋₄ alkyl, preferably hydrogen, and ba isfrom 1 to 6, preferably 2 or 3, and ca is from 1 to 12, preferably 1 to6.

Preferred groups B¹ include a valence bond and alkylene, oxaalkylene andoligo-oxaalkylene groups of up to 12 carbon atoms.

Preferably B and B¹ are the same.

When X is a group of formula (IVC) preferably B is a group of formula--[(CR⁴ ₂ CR⁴ ₂)_(c) O_(b) ]CR⁴ ₂ CR⁴ ₂ --, eg. --(CH₂ CH₂ O)_(c) (CH₂CH₂)--.

The groups of formula (IVD) are: ##STR6## wherein the groups R⁹ are thesame or different and each is hydrogen or C₁ -C₄ alkyl, R^(9a) is ahydrogen or, more preferably, a group --C(O)B² R^(9b), R^(9b) ishydrogen or methyl, preferably methyl, B² is a valence bond or astraight or branched alkylene, oxaalkylene or oligo-oxaalkylene group,and g is from 1 to 4; and

if B is other than a valence bond z is 1 and if B is a valence bond z isO if X is directly bonded to an oxygen or nitrogen atom and otherwise zis 1.

Preferably the groups R⁹ are the same. It is also preferable that atleast one of the groups R⁹ is methyl, and more preferable that thegroups R⁹ are all methyl.

Preferably g is 1 or 2, more preferably 2.

Preferably B² is:

a valence bond;

an alkylene group of formula --(CR^(3b) ₂)_(ab) --, wherein the groups--(CR^(3b) ₂)-- are the same or different, and in each group --(CR^(3b)₂)-- the groups R^(3b) are the same of different and each group R^(3b)is hydrogen or C₁₋₄ alkyl, preferably hydrogen, and ab is from 1 to 12,preferably 1 to 6;

an oxaalkylene group such as alkoxyalkyl having 1 to 6, carbon atoms ineach alkyl moiety, more preferably --CH₂ O(CH₂)₄ --; or

an oligo-oxaalkylene group of formula --[(CR^(4b) ₂)_(bb) O]_(cb) --where the groups --(CR^(4b) ₂)-- are the same or different and in eachgroup --(CR^(4b) ₂)-- the groups R^(4b) are the same or different andeach group R b is hydrogen or C₁₋₄ alkyl, preferably hydrogen, and bb isfrom 1 to 6, preferably 2 or 3, and cb is from 1 to 12, preferably 1 to6.

Preferred groups B² include a valence bond and alkylene, oxalkylene andoligo-oxalkylene groups of up to 12 carbon atoms.

Preferably B and B² are the same.

When X is a group of formula (IVD) preferably B is a group of formula--[(CR⁴ ₂ CR⁴ ₂)_(b) O]_(c) CR⁴ ₂ CR⁴ ₂ --, eg. --(CH₂ CH₂ O)_(c) CH₂CH₂ --.

The groups of formula (IVE) are: ##STR7## wherein the groups R¹⁰ are thesame or different and each is hydrogen or C₁₋₄ alkyl, R^(10a) ishydrogen or, more preferably, a group --C(O)B³ R^(10b) where R^(10b) ishydrogen or methyl, preferably methyl, B³ is a valence bond or astraight or branched alkylene, oxaalkylene or oligo-oxaalkylene group,and h is from 1 to 4; and

if B is other than a valence bond z is 1 and if B is a valence bond z isO if X is directly bonded to the oxygen or nitrogen and otherwise z is1.

Preferably the groups R are the same. It is also preferable that atleast one of the groups R¹⁰ is methyl, and more preferable that thegroups R¹⁰ are all methyl.

Preferably h is 1 or 2, more preferably 2.

Preferably B³ is:

a valence bond;

an alkylene group of formula --(CR^(3c) ₂)_(ac) --, wherein the groups--(CR^(3c) ₂)-- are the same or different, and in each group --(CR^(3c)₂)-- the groups R^(3c) are the same or different and each group R^(3c)is hydrogen or C₁₋₄ alkyl, preferably hydrogen, and ac is from 1 to 12,preferably 1 to 6;

an oxaalkylene group such as alkoxyalkyl having 1 to 6 carbon atoms ineach alkyl moiety, more preferably --CH₂ O(CH₂)₄ --; or

an oligo-oxaalkylene group of formula --[(CR^(4c) ₂)_(bc) O]_(cc) --where the groups --(CR^(4c) ₂)-- are the same or different and in eachgroup --(CR^(4c) ₂)-- the groups R^(4c) are the same or different andeach group R^(4c) is hydrogen or C₁₋₄ alkyl, preferably hydrogen, and bcis from 1 to 6, preferably 2 or 3, and cc is from I to 12, preferably 1to 6.

Preferred groups B³ include a valence bond and alkylene, oxaalkylene andoligo-oxaalkylene groups of up to 12 carbon atoms.

Preferably B and B³ are the same.

When X is a group of formula (IVE) preferably B is a group of formula--](CR⁴ ₂ CR⁴ ₂)_(b) O]_(c) CR⁴ ₂ CR⁴ ₂ --, eg. --(CH₂ CH₂ O)_(c) CH₂CH₂ --.

Further zwitterionic groups are of formula (VA), (VB) and (VC). Thesegroups also contain an alkyl, fluoroalkyl or siloxane group. Monomerscontaining such a group are therefore particularly suitable for use inpolymers without separate comomoners containing a hydrophobic group.

The groups of formula (VA) are: ##STR8## wherein the groups R¹¹ are thesame or different and each is hydrogen or C₁₋₄ alkyl, R^(11a) is either

(a) a group --[C(O)]_(vw) (CR^(11b) ₂)_(ww) (SiR^(11c) ₂) (OSiR^(11c)₂)_(vv) R^(11c) in which each group R^(11b) is the same or different andis hydrogen or alkyl of 1 to 4 carbon atoms, each group R^(11c) is thesame or different and is alkyl of 1 to 4 carbon atoms or aralkyl, forexample benzyl or phenethyl, vw is 0 or 1, ww is from 0 to 6 with theproviso that vw and ww are not both 0, and vv is from 0 to 49;

(b) a group of formula --C(O)B⁴ --R^(11d), in which R^(11d) is hydrogenor methyl, B⁴ is a valence bond or straight or branched alkylene,oxaalkylene or oligo-oxaalkalyene group optionally containing one ormore fluorine atoms, and containing from 6 to 24, preferably 6 to 18carbon atoms;

i is from 1 to 4; and

if B is other than a valence bond z is 1 and if B is a valence bond z is0 if X is directly bonded to an oxygen or nitrogen atom and otherwise zis 1.

Preferably the groups R¹¹ are the same. It is also preferable that atleast one of the groups R¹¹ is methyl, and more preferable that thegroups R¹¹ are all methyl.

Preferably i is 1 or 2, more preferably 2.

Where R^(11a) is a siloxane group as defined in (a) above, each group(CR^(11b) ₂) may be the same or different, preferably the same, andpreferably each group R^(11b) is hydrogen. Preferably ww is from 2 to 4,and is most preferably 3 when vw is 0 or 2 when vw is 1. Each group(SiR^(11c) ₂) may be the same or different, preferably the same, andpreferably each group R^(11c) is methyl. Preferably vv is from 4 to 29.

Preferably the group R^(11a) is a group --C(O)B⁴ R^(11d) as definedabove. In such a case, preferably B⁴ is:

a valence bond;

an alkylene group of formula --(CR^(3d) ₂)_(ad) --, wherein the groups--(CR^(3d) ₂)-- are the same or different, and in each group --(CR^(3d)₂)-- the groups R^(3d) are the same or different and each group R^(2d)is hydrogen, fluorine or C₁₋₄ alkyl or fluoroalkyl, preferably hydrogenor fluorine, and ad is from 1 to 24, preferably 6 to 18;

an oxaalkylene group such as alkoxyalkyl having 1 to 6 carbon atoms andoptionally one or more fluorine atoms in each alkyl moiety, or

an oligo-oxalkylene group of formula --[(CR^(4d) ₂)_(bd) O]_(cd) --where the groups --(CR^(4d) ₂)-- are the same or different and in eachgroup --(CR^(4d) ₂)-- the groups R^(4d) are the same or different andeach group R d is hydrogen, fluorine or C₁₋₄ alkyl or fluoroalkyl,preferably hydrogen or fluorine, and bd is from 2 to 6, preferably 3 or4, and cd is from 1 to 12, preferably 1 to 6.

In one embodiment B and B⁴ may be the same.

The groups of formula (VB) are: ##STR9## wherein the groups R¹² are thesame or different and each is hydrogen or C₁ -C₄ alkyl, R^(12a) iseither

(a) a group --[C(O)]_(tu) (CR^(12b) ₂)_(uu) (SiR^(12c) ₂) (OSiR^(12c)₂)_(tt) R^(12c) in which each group R^(12b) is the same or different andis hydrogen or alkyl of 1 to 4 carbon atoms, each group R^(12c) is thesame or different and is alkyl of 1 to 4 carbon atoms or aralkyl, forexample benzyl or phenethyl, tu is 0 or 1, uu is from 0 to 6, with theproviso that tu and uu are not both 0, and tt is from 0 to 49; or

(b) a group of formula --C(O)B⁵ --R^(12d), in which R^(12d) is hydrogenor methyl, B⁵ is a valence bond or a straight or branched alkylene,oxaalkylene or oligo-oxaalkylene group optionally containing one or morefluorine atoms and from 6 to 24 carbon atoms, more preferably 6 to 18carbons atoms,

j is from 1 to 4; and

if B is other than a valence bond, z is 1 and if B is a valence bond zis 0 if X is directly bonded to an oxygen or nitrogen atom and otherwisez is 1.

Preferably the groups R¹² are the same. It is also preferable that atleast one of the groups R¹² is methyl, and more preferable that thegroups R¹² are all methyl.

Preferably j is 1 or 2, more preferably 2.

Where R^(12a) is a siloxane group as defined in (a) above, each group(CR^(12b) ₂) may be the same or different, preferably the same, andpreferably each group R^(12b) is hydrogen. Preferably uu is from 2 to 4,and is most preferably 3 when tu is 0 or 2 when tu is 1. Each group(SiR^(12c) ₂) may be the same or different, preferably the same, andpreferably each group R^(12c) is methyl. Preferably tt is from 4 to 29.

Preferably the group R^(12a) is a group --C(O)B⁴ R^(12d) as definedabove. In such a case, preferably B⁵ is:

a valence bond;

an alkylene group of formula --(CR^(3e) ₂)_(ee) --, wherein the groups--(CR^(3e) ₂)-- are the same or different, and in each group --(CR^(3e)₂)-- the groups R^(3e) are the same of different and each group R^(3e)is hydrogen, fluorine or C₁₋₄ alkyl, or fluoroalkyl, preferably hydrogenor fluorine, and ae is from 1 to 24, preferably 6 to 18;

an oxaalkylene group such as alkoxyalkyl having 1 to 6 carbon atoms andoptionally one or more fluorine atoms in each alkyl moiety; or

an oligo-oxaalkylene group of formula --[(CR^(4e) ₂)_(be) O]_(ce) --where the groups --(CR^(4e) ₂)-- are the same or different and in eachgroup --(CR^(4e) ₂)-- the groups R_(4e) are the same or different andeach group R^(4e) is hydrogen, fluorine or C₁₋₄ alkyl or fluoroalkyl,preferably hydrogen or fluorine, and be is from 2 to 6, preferably 3 or4, and ce is from 1 to 12, preferably 1 to 6.

In one embodiment B and B⁵ may be the same.

The groups of formula (VC) are: ##STR10## wherein the groups R¹³ are thesame or different and each is hydrogen or C₁₋₄ alkyl, R^(13a) is either

(a) a group --[C(O)]_(rs) (CR^(13b) ₂)_(ss) (SiR^(13c) ₂) (OSiR^(13c)₂)_(rr) R^(13c) in which each group R^(13b) is the same or different andis hydrogen or alkyl of 1 to 4 carbon atoms, each group R^(13c) is thesame or different and is alkyl of 1 to 4 carbon atoms or aralkyl, forexample benzyl or phenethyl, rs is 0 or 1, ss is from 0 to 6, with theproviso that rs and ss are not both 0, and rr is from 0 to 49; or

(b) a group of formula --C(O)B⁶ --R^(13d), in which R^(13a) is hydrogenor methyl, B⁶ is a valence bond or a straight or branched alkylene,oxaalkylene or oligo-oxaalkylene group optionally containing one or morefluorine atoms and from 6 to 24, more preferably 6 to 18 carbon atomsand k is from 1 to 4; and

if B is other than a valence bond, Z is 1 and if B is a valence bond Zis 0 if X is directly bonded to an oxygen or nitrogen atom and otherwiseZ is 1.

Preferably the groups R¹³ are the same. It is also preferable that atleast one of the groups R¹³ is methyl, and more preferable that thegroups R¹³ are all methyl.

Preferably k is 1 or 2, more preferably 2.

Where R^(13a) is a siloxane group as defined in (a) above, each group(CR^(13b) ₂) may be the same or different, preferably the same andpreferably each group R^(13b) is hydrogen. Preferably ss is from 2 to 4,and is most preferably 3 when rs is 0 or 2 when rs is 1. Each group(SiR^(13c) ₂) may be the same, or different, preferably the same, andpreferably each group R^(13c) is methyl. Preferably rr is from 4 to 29.

Preferably the group R^(13a) is a group --C(O)B⁶ R^(13d) as definedabove. In such a case, preferably B⁶ is:

a valence bond;

an alkylene group of formula --(CR^(3f) ₂)_(af) --, wherein the groups--(CR^(3f) ₂)-- are the same or different, and in each group --(CR^(3f)₂)-- the groups R^(3f) are the same or different and each group R^(3f)is hydrogen, fluorine or C₁₋₄ alkyl or fluoroalkyl, preferably hydrogenor fluorine, and is from 1 to 24, preferably 6 to 18;

an oxaalkylene group such as alkoxyalkyl having 1 to 6 carbon atoms andoptionally one or more fluorine atoms in each alkyl moiety; or

an oligo-oxaalkylene group of formula --[(CR^(4f) ₂)_(bf) O]_(cf) --where the groups --(CR^(4f) ₂)-- are the same or different and in eachgroup --(CR^(4f) ₂)-- the groups R^(4f) are the same or different andeach group R^(4f) is hydrogen, fluorine or C₁₋₄ alkyl or fluoroalkyl,preferably hydrogen or fluorine, and bf is from 2 to 6, preferably 3 or4, and cf is from 1 to 12, preferably 1 to 6.

In one embodiment B and B⁶ may be the same.

Particular examples of preferred monomers containing a zwitterionicgroup are 2-(methacryloyloxy)ethyl-2'-(trimethylammonium)ethyl phosphateinner salt and 1[4(4'-vinylbenzyloxy)butane]-2'(trimethylammonium) ethylphosphate inner salt.

Monomers containing a zwitterionic group such as those of formula (II)and (III) may be prepared by conventional techniques using knownreactions, for example using a suitable substituted alkyl (alk)acrylateor suitable substituted styrene as precursor. Examples of suitablesubstituted alkyl (alk)acrylates includedimethylaminoethyl(meth)acrylate and 2-hydroxyethyl(meth)acrylate.

Monomers of formula (II) or (III) containing a group of formula (IVA) or(IVB) may be prepared as described in the Reference Examples herein orby analogous known methods.

Monomers of formula (II) or (III) containing a group of formula (IVC) inwhich R^(8a) is --C(O)B¹ R^(8b) may be prepared by selective acylationof glycerophosphorylcholine or analogues thereof at the primary hydroxylgroup with an activated acid derivative such as an acid anhydrideO(C(O)B¹ R^(8b)), or an acid halide R^(8b) B¹ COHal where B¹ and R^(8b)are as defined above and Hal is halogen, followed by acylation of thesecondary hydroxyl group with an appropriate acylating agent, forexample methacryloyl chloride. Purification, for example by columnchromatography on a suitable support, may be performed after eachacylation or after the second acylation only. Suitable activated acidderivatives include acid anhydrides, acid halides, reactive esters andimidazolides. The acylations may be performed in a suitable anhydrous,aprotic solvent, for example N,N-dimethylformamide, optionally in thepresence of a suitable non-nucleophilic base, for example triethylamine.

Alternatively, the primary alcohol group in glycerophosphoryl choline oran analogue thereof may be blocked by reaction with a suitableprotecting group reagent, for example t-butyldimethylsilyl chloride,under standard conditions and the secondary hydroxy group then treatedwith an acylating agent such as methacryloyl chloride. Thet-butyldimethylsilyl protecting group may be removed by treatment with adilute organic or mineral acid, for example p-toluene sulphonic acid,hydrochloric acid or with tetra-butylammonium fluoride. The deblockedprimary hydroxyl group may then be treated with an activated acidderivative such as an acid anhydride O(C(O)B¹ R^(8b))₂ or acid halideR^(8b) B¹ COHal where B¹ and R^(8b) are as defined above, and Hal ishalogen.

Analogues of glycerophosphorylcholine (compounds of formula (II) or(III) containing a group (IVD) where R^(8a) is hydrogen) may be preparedby reaction of phosphorus oxychloride with a bromoalcohol in an inertaprotic solvent, such as dichloromethane, to give abromoalkylphosphorodichloridate. The dichloro derivative thus producedmay then be treated with an appropriately protected glycerol derivative,f or example 2,2-dimethyl 1,3-dioxolane-4-methanol, in the presence of abase, for example triethylamine, followed by acid hydrolysis to give abromoalkylphosphoro-glycerol derivative. This may then be treated withan amine NR⁸ ₃, where R⁸ is as defined above, for exampletrimethylamine, to generate the glycerophosphorylcholine analogue. Thispreparation is depicted in the following scheme. ##STR11##

where R⁸ and f are as defined in relation to groups of formula (IVC).

Monomers of formula (II) or (III) containing a group of formula (IVD) inwhich R^(9a) is --C(O)B² R^(9b) may be prepared by the selectiveacylation of glycerophosphorylcholine or an analogue thereof at theprimary hydroxyl group with for example, methacryloyl chloride followedby reaction at the secondary hydroxyl group using an activated acidderivative, such as an acid halide O(C(O)B² R^(9b))₂ or an acid halideR^(9b) B² COHal, where B² and R^(9b) are as defined above and Hal ishalogen. The intermediates and final products may be purified, asnecessary using column chromatography. Optionally, protecting groupstrategy, similar to that outlined above in relation to production ofmonomers containing a group of formula (IVC) may be employed.

Monomers of formula (II) or (III) containing a group of formula (IVE)may be prepared in an analogous manner to monomers containing groups offormula (IVD) or (IVE).

Monomers of formula (II) or (III) containing a group of formula (VA),(VB) or (VC) may be prepared by direct analogy with methods describedfor monomers containing groups of formula (IVC), (IVD) and (IVE)respectively.

A.2. Comonomers, for instance containing a hydrophobic, reactive orionic group

The polymer (A) containing pendant zwitterionic groups preferablycomprises residues of a further comonomer containing a hydrophobic,functional or ionic group as well as the residues of the comonomercontaining a zwitterionic group. The presence of such addition comonomerresidues may modify the properties of the copolymer to improve itscompatibility with the polymer (B) in the blends of the invention.

It will be appreciated that in some circumstances it may be desirable touse a combination of different comonomers containing different types ofgroups. Preferably a comonomer of type a), b) and/or c) as defined belowor a combination of such comonomers is used, more preferably only one ofcomonomer types a), b) and c) is used.

A.2.a. Comonomers containing an alkyl, fluoroalkyl or siloxane group

The comonomers containing an alkyl-based group for instance ahydrophobic group, or one which contains for instance a fluoroalkyl orsiloxane group, are comonomers containing

a) an alkyl group which group optionally contains one or more ethericoxygen atoms and optionally one or more carbon-carbon double or triplebonds for instance which has 6 or more carbon atoms, or

b) a fluoroalkyl group, preferably of 6 or more carbon atoms, whichgroup optionally contains one or more etheric oxygen atoms andoptionally one or more carbon-carbon double or triple bonds, or

c) a siloxane group, containing up to 50 silicon atoms, preferably in alinear chain.

Preferably the alkyl or fluoroalkyl groups contains up to 24 carbonatoms, for instance up to 18 carbon atoms. Preferred comonomerscontaining an alkyl, fluoroalkyl or siloxane group are those of generalformula (VI)

    Y.sup.1 --Q                                                (VI)

where Y¹ is an ethylenically unsaturated polymerisable group selectedfrom ##STR12## where R¹⁴ is hydrogen or C₁ -C₄ alkyl, A' is --O-- or--NR¹⁵ -- where R¹⁵ is hydrogen or a C₁ -C₄ alkyl group or R¹⁵ is agroup Q;

K¹ is a group --(CH₂)₁ OC(O)--, (CH₂), C(O)O, --(CH₂)₁ OC(O)O--,--(CH₂)₁ NR¹⁶ --, --(CH₂)₁ NR¹⁶ C(O)--, --(CH₂)₁ C(O)NR¹⁶ --, --(CH₂)₁NR¹⁶ C(O)O--, --(CH₂)₁ OC(O)NR¹⁶ --, --(CH₂)₁ NR¹⁶ C(O)NR¹⁶ -- (in whichthe groups R¹⁶ are the same or different), --(CH₂)₁ O--, --(CH₂)SO₃ --,a valence bond and 1 is from 1 to 12 and R¹⁶ is hydrogen or a C₁ -C₄alkyl group; and

Q is (a) a straight or branched alkyl, alkoxyalkyl or(oligo-alkoxy)alkyl chain containing, for instance preferably 6 to 24,carbon atoms unsubstituted or substituted by one or more fluorine atomsand optionally containing one or more carbon-carbon double or triplebonds; or

(b) a siloxane group --(CR^(16a) ₂)_(qq) (SiR^(16b) ₂) (OSiR^(16b)₂)_(pp) R^(16b) in which each group R^(16a) is the same or different andis hydrogen or alkyl of 1 to 4 carbon atoms or aralkyl, for examplebenzyl or phenethyl, each group R^(16b) is alkyl of 1 to 4 carbon atoms,qq is from 1 to 6 and pp is from 0 to 49.

Preferred comonomers of formula (VI) bearing a group Q include those offormula (VII) and (VIII): ##STR13## wherein: R¹⁴, A', K¹ and Q are asdefined in relation to formula (VI).

Preferably in the compounds of formula (VII) R¹⁴ is hydrogen methyl orethyl, more preferably methyl so that the compound of formula (VII) ispreferably an acrylic acid, methacrylic acid or ethacrylic acidderivative.

In the compounds of formula (VIII) K¹ may for instance be a valencebond. Where K¹ is a group then preferably 1 is from 1 to 6, morepreferably 1, 2 or 3 and most preferably 1 is 1. When K¹ is a group--(CH₂)₁ NR¹⁶ --, --(CH₂)₁ OC(O)NR¹⁶ --, --(CH₂)₁ NR¹⁶ C(O)O--, --(CH₂)₁NR¹⁶ C(O)--, --(CH₂)₁ C(O)NR¹⁶ -- or --(CH₂)₁ NR¹⁶ C(O)NR¹⁶ -- then R¹⁶is preferably hydrogen, methyl or ethyl, more preferably hydrogen.

In the compounds of formula (VIII), preferably the vinyl group is parato the group --K¹ --Q.

Preferably Q is an alkyl or fluoroalkyl group optionally containing oneor more etheric oxygen atoms and optionally one or more carbon-carbondouble or triple bonds. More preferably Q is:

an alkyl group of formula --(CR¹⁷ ₂)_(m) CR¹⁷ ₃ wherein the groups--(CR¹⁷ ₂)-- are the same or different, and in each group --(CR¹⁷ ₂)--the groups R¹⁷ are the same or different and each group R¹⁷ is hydrogen,fluorine or C₁₋₄ alkyl or fluoroalkyl and m is from 5 to 23 if Qcontains no fluorine atoms or from 1 to 23, preferably 5 to 23, if Qcontains one or more fluorine atoms;

an alkoxyalkyl having 1 to 12 carbon atoms in each alkyl moiety;unsubstituted or substituted by one or more fluorine atoms; or

an (oligo-alkoxyl) alkyl group of formula --[(CR¹⁸ ₂)_(n) O]_(o) (CR¹⁸₂)_(n) R¹⁸ where the groups --(CR¹⁸ ₂)-- are the same or different andin each group --(CR¹⁸ ₂)-- the groups R¹⁸ are the same or different andeach group R¹⁸ is hydrogen, fluorine or C₁₋₄ alkyl or fluoroalkyl and nis from 2 to 6, preferably 3 to 4, and o is from 1 to 12.

Alternatively, Q may be a group in which one or more of the alkyl oralkylene moieties in such an alkyl, alkoxyalkyl or (oligoalkoxy) alkylgroup is replaced by a corresponding alkenyl, alkynyl, alkenylene oralkynylene moiety.

Preferred groups Q include alkyl, alkoxyalkyl and (oligo-alkoxy)alkylgroups optionally containing one or more carbon-carbon double or triplebonds of 8 or more, more preferably 10 or more, even more preferably 12or more, for instance 14 or more, such as 16 or more carbon atoms. Suchgroups may contain one or more fluorine atoms and be thereforefluoroalkyl derivatives. Preferably however, such groups do not containany fluorine atoms.

Particularly preferred groups are straight chain alkyl or fluoroalkylgroups optionally containing one or more carbon-carbon double or triplebonds.

Where Q is a siloxane group, each group --(CR^(16a) ₂)-- may be the sameor different, preferably the same, and preferably each group R^(16a) ishydrogen. Preferably qq is from 2 to 4, and is most preferably 3. Eachgroup --(SiR^(16b) ₂)-- may be the same or different, preferably thesame, and preferably each group R^(16b) is methyl. Preferably pp is from4 to 29. Preferred comonomers where Q is a siloxane group are those offormula (VII).

In one specific embodiment the group Q does not contain any ethylenicunsaturation, i.e. any carbon-carbon double or triple bonds.

Particular examples of comonomers containing an alkyl, fluoroalkyl orsiloxane group include: methylmethacrylate, butylmethacrylate, n-dodecylmethacrylate, octadecyl methacrylate, hexadecyl methacrylate,1H,1H,2H,2H-heptadecafluorodecyl methacrylate, p-octyl styrene,p-dodecyl styrene and monomethacryloxypropyl terminated siloxanes.n-Dodecyl methacrylate is particularly preferred.

Comonomers containing an alkyl or fluoroalkyl, which does not contain acarbon-carbon double or triple bond, or a siloxane group such as thoseof formulae (VII) and (VIII) are commercially available or may beprepared by conventional techniques using known reactions.

In a second specific embodiment of such comonomers, the group Q doescontain ethylene unsaturation, i.e. one or more carbon-carbon double ortriple bonds. Such comonomers may for example contain a vinylic,divinylic, acetylenic or diacetylenic moiety. Comonomers containingacetylenic rather than vinylic unsaturation are in general preferred,especially those containing a single acetylenic group.

Comonomers which contain such an ethylenic unsaturated group, which doesnot react in the initial polymerisation reaction but which can besubsequently activated, are capable of providing crosslinking betweenlinear polymer chains once the polymer is blended with a polymer (B).Such crosslinking through reaction of ethylenic or acetylenic pendantgroups of the polymer A with other groups on polymer A molecules or onpolymer B molecules may improve the stability of the blend and istypically formed by irradiation, for example with UV- orgamma-radiation. The crosslinking of such groups may be employed eitheralone or in addition to the use of a comonomer containing a reactivegroup as a crosslinkable comonomer as described below.

Particularly preferred crosslinkable comonomers containing a hydrophobicgroup are those of formula (VIIA) and (VIIIA). ##STR14## in which R¹⁴,A' and K¹ are as hereinbefore defined and QQ is an alkynyl groupcontaining 6 or more carbon atoms and one or two, preferably one,carbon-carbon triple bonds provided that the acetylenic moieties are notdirectly bonded to A' or K¹.

Amongst such comonomers it is preferred that QQ is a group containingfrom 6 to 24 carbon atoms, preferably 8 or more, more preferably 10 ormore, even more preferably 12 or more, for instance 14 or more, such as16 or more carbon atoms.

It is also preferred that the group QQ does not contain a terminalacetylenic moiety, i.e. a group --C.tbd.CH.

A particularly preferred group QQ is 7-dodecynyl and a specific exampleof a compound of formula (VIIA) containing such a group is dodec-7-ynylmethacrylate.

The compounds of formula (VIIA) and (VIIIA) and other comonomers offormula (VII) and (VIII) containing an ethylenically unsaturatedphysisorbable group Q, may be prepared by analogy with known methods.Their preparation is illustrated by Reference Example 5.

A.2. (b Comonomers bearing a reactive group

Preferred comonomers, which contain a reactive functional group capableof providing crosslinking within the polymer (A) or to the polymer (B)and/or providing reactive groups on the surface of the blend of theinvention are of general formula (IX)

    Y.sup.2 --Q.sup.1                                          (IX)

where Y² is an ethylenically unsaturated polymerisable group selectedfrom ##STR15## where R¹⁹ is hydrogen or C₁ -C₄ alkyl, K² is a group--(CH₂)_(q) OC(O)--, --(CH₂)_(q) C(O)O--, --(CH₂)_(q) OC(O)O--,--(CH₂)_(q) NR²⁰ --, --(CH₂)_(q) NR²⁰ C(O)--, --(CH₂)_(q) C(O)NR²⁰ --,--(CH₂)_(q) NR²⁰ C(O)O--, --(CH₂)_(q) OC(O)NR²⁰ --, --(CH₂)_(q) NR²⁰C(O)NR²⁰ -- (in which the groups R²⁰ are the same or different),--(CH₂)_(q) O--, or --(CH₂)_(q) SO₃ --, or a valence bond and q is from1 to 12 and R²⁰ is hydrogen or a C₁ -C₄ alkyl group; and

Q¹ is a reactive group capable of reacting to provide crosslinkingwithin the polymer (A) or to the polymer (B) and/or providing a reactivegroup on the surface of the blend.

Preferred comonomers of formula (IX) bearing a reactive group Q¹ includethose of formula (X) and (XI) defined below.

The compounds of formula (X) are: ##STR16## wherein: R¹⁹ is as definedwith reference to formula (X), and

Q² is a reactive group.

Preferably in the compounds of formula (X) R¹⁹ is hydrogen, methyl orethyl, more preferably methyl, so that the compound of formula (X) ispreferably an acrylic acid, methacrylic acid or ethacrylic acidderivative.

Preferably Q is hydrogen, or more preferably --OH or a group of theformula:

    --T--B.sup.7 --Q.sup.3

where T is --O--, or --NR²¹ -- where R²¹ is hydrogen, C₁ -C₄ alkyl or agroup --B⁷ --Q³ ;

B is a valence bond or, more preferably, a straight or branchedalkylene, oxaalkylene or oligo-oxaalkylene chain; and

Q³ is a reactive group such as an aldehyde group or a silane or siloxanegroup containing one or more reactive substituents such as halogen, forexample chlorine, or alkoxy, generally containing from 1 to 4 carbonatoms, for example methoxy or ethoxy, or, more preferably Q³ is ahydroxyl, amino, carboxyl, epoxy, --CHOHCH₂ Hal, (in which Hal is ahalogen atom such as chlorine, bromine or iodine) succinimido, sulphonicacid esters such as tosylate and triflate, imidazole carbonyl-amino, oran optionally substituted triazine group.

Preferably B⁷ is:

an alkylene group of formula --(CR²² ₂)_(r) --, wherein the groups--(CR²² ₂)-- are the same or different, and in each group --(CR²² ₂)--the groups R²² are the same or different and each group R²² is hydrogenor C₁₋₄ alkyl, preferably hydrogen, and r is from 1 to 12, preferably 1to 6;

an oxaalkylene group such as alkoxyalkyl having 1 to 6 carbon atoms ineach alkyl moiety; or

an oligo-oxaalkylene group of formula --[(CR²³ ₂)_(s) O_(t) (CR²³ ₂)_(s)-- where the groups --(CR²³ ₂)-- are the same or different and in eachgroup --(CR²³ ₂)-- the groups R²³ are the same or different and eachgroup R²³ is hydrogen or C₁₋₄ alkyl, preferably hydrogen, and s is from1 to 6, preferably 2 or 3, and t is from 1 to 11, preferably 1 to 5.

Preferred groups B⁷ include alkylene, oxaalkylene and oligo-oxaalkylenegroups of up to 12 carbon atoms.

Where Q³ is a silane or siloxy group, preferably B⁷ is an alkylene groupof 1 to 6, preferably 2 to 4, more preferably 3 carbon atoms.

Particular examples of the group B⁷ are --CH₂ --, --CH₂ CH₂ -- and--(CH₂)₆ --.

The compounds of formula (XI) are: ##STR17## wherein K² is as defined inrelation to formula (IX) and; B⁸ is a straight of branched alkylene,oxaalkylene or oligo-oxaalkylene chain and

Q⁴ is a reactive group, for example an aldehyde group or a silane orsiloxane group containing one or more reactive substituents such ashalogen, for example chlorine, or alkoxy, generally containing from 1 to4 carbon atoms, for example methoxy or ethoxy, or, more preferably, Q⁴is a hydroxyl, amino, carboxyl, epoxy, --CHOHCH₂ Hal, (in which Hal is ahalogen atom such as chlorine, bromine or iodine) succinimido, tosylate,triflate, imidazole carbonyl-amino or optionally substituted triazinegroup.

In the compounds of formula (XI) preferably the vinyl group is para tothe group --K² --B⁸ --Q⁴.

K² may for instance be a valence bond. Where K² is a group thenpreferably q is from 1 to 6, more preferably 1,2 or 3 and mostpreferably q is 1. When K² is a group --(CH₂)_(q) NR²⁰ --, --(CH₂)_(q)OC(O)NR²⁰ --, --(CH₂)_(q) NR²⁰ C(O)O--, --(CH₂)_(q) NR²⁰ C(O)--,--(CH₂)_(q) C(O)NR²⁰ -- or --(CH₂)_(q) NR²⁰ C(O)NR²⁰ -- then R²⁰ ispreferably hydrogen, methyl or ethyl, more preferably hydrogen.

Preferably B⁸ is:

an alkylene group of formula --(CR²⁴ ₂)_(u) --, wherein the groups--(CR²⁴ ₂)-- are the same or different, and in each group --(CR²⁴ ₂)--the groups R²⁴ are the same of different and each group R²⁴ is hydrogenor C₁₋₄ alkyl, preferably hydrogen, and u is from 1 to 12, preferably 1to 6;

an oxaalkylene group such as alkoxyalkyl having 1 to 6 carbon atoms ineach alkyl moiety; or

an oligo-oxaalkylene group of formula --[(CR²⁵ ₂)_(v) O]_(w) (CR²⁵)_(v)-- where the groups --(CR²⁵ ₂)-- are the same or different and in eachgroup --(CR²⁵ ₂)-- the groups R²⁵ are the same or different and eachgroup R²⁵ is hydrogen or C₁₋₄ alkyl, preferably hydrogen, and v is from1 to 6, preferably 2 or 3, and w is from 1 to 12, preferably 1 to 6.

Preferred groups B⁸ include alkylene, oxaalkylene and oligo-oxaalkylenegroups of up to 12 carbon atoms. In one embodiment B⁸ and K² containtogether up to 12 carbon atoms.

Particular examples of comonomers bearing a reactive group includechloromethylstyrene, methacrylic acid, 2-aminoethylmethacrylate,2,3-epoxypropyl methacrylate, 3-chloro-2-hydroxypropylmethacrylate,2-methacryloyloxyethyl-dichloro-1,3,5-triazine,3-chloro-2-hydroxy-propylmethacrylamide and glycidyl methacrylate andreactive methacrylate esters containing the group HetC(O)O--in which(Het) is a heterocyclic ring, for example benzotriazole or imidazole andreactive methacrylate esters containing a group R¹⁶ OC(O)--in which R¹⁶is a succinimido or pentafluorophenyl group.

Particularly preferred comonomers bearing reactive groups are2-aminoethyl-methacrylate and 3-chloro-2-hydroxypropylmethacrylate.

Comonomers bearing a reactive group such as those of formula (X) or(XI), are commercially available or may be prepared by conventionaltechniques using known reactions.

Comonomers of formula (X), which are dichlorotriazine monomers may beprepared in known manner for example by reacting a substitutedhydroxy-alkyl(alk)acrylate or aminoalkyl(alk)acrylate withtrichlorotriazine in a suitable solvent and in the presence of a base.

Comonomers of formula (XI) which are reactive methacrylate esters inwhich the ester groups contains an imidazole group may be prepared inknown manner by reacting a substituted hydroxyalkyl(alk)acrylate (e.g.2-hydroxyethyl-(meth)acrylate), polyethylene-oxide(meth)acrylate orpolypropyleneoxide (meth)acrylate with 1,1-carbonyl-diimidazole in a drysolvent. Analogous known methods may be used to prepare succinimido andpentafluorophenyl methacrylate esters of formula (X), by reaction with areactive ester, acid halide or acid anhydride.

Reactive groups may provide points for the attachment of moieties suchas ligands to the surface of the polymer blend.

Comonomers containing a reactive group, such as compounds of formula (X)and (XI) may also be used as comonomers containing crosslinkable groups(i.e. coreactive groups), which react with other crosslinkable groups(or coreactive groups), either in the polymer (A) or the polymer (B).

Where comonomers containing a reactive group are used to provide suchcrosslinkable groups then the crosslinkable groups and/or thecopolymerisation conditions will be chosen so that they will notcrosslink when the comonomers are copolymerised; thus the polymerisationproduct will be an uncrosslinked linear copolymer which may besubsequently crosslinked after blending the copolymer with polymer (B)so as to improve the stability of the bland. When such crosslinkingbetween linear polymer chains is employed the crosslinkage may be formedeither between two such crosslinkable groups or between a crosslinkablegroup and a non-inert group mutually coreactive in a diluent comonomerresidue (defined later). Such a crosslinkage may be formed either bydirect reaction of the groups forming the crosslinkage or by reaction ofthese groups with a reactive bridging molecule for example a reactivegas, such as ammonia.

Residues of such comonomers may therefore be present in polymers whichalso contain residues of comonomers containing a hydrophobic group suchas those of formula (VA), (VB) or (VC) or a comonomer containing analkyl, fluoroalkyl or siloxane group, which is of formula (VII) or(VIII). Similarly residues of such comonomers may also be present incopolymers which contains residues of a compound containing an ionicgroup of formula (XIII) or (XIV) as defined below.

Preferred reactive comonomers which are used to crosslink the comonomer,are those of formula (X) or (XI) in which Q², or Q⁴ contains acrosslinkable cinnamyl, epoxy, --CHOHCH₂ Hal (in which Hal is a halogenatom), methylol, silyl, an ethylenically unsaturated crosslinkablegroup, such as an acetylenic, diacetylenic, vinylic or divinylic group,or an acetoacetoxy or chloroalkyl sulfone, preferably chloroethylsulphone, group.

Particular examples of comonomers bearing a group capable ofcrosslinking include methacrolein, cinnamyl methacrylate,2,3-epoxypropyl methacrylate, 3-chloro-2-hydroxypropyl methacrylate,hydroxymethyl methacrylamide, 3-(trimethoxysilyl)propyl methacrylate,2-acetoacetoxyethyl methacrylate, 3-(vinylbenzyl)-2-chloroethyl sulfone.

When a polymer (A) containing crosslinkable groups, is blended with apolymer (B) the polymer (A) is preferably in substantially uncrosslinkedform. After blending and optionally after additional processing steps,crosslinking of crosslinkable groups may be performed to increase thestrength and stability of the blend. Such crosslinking may for examplebe performed upon the final processed and shaped blend.

A.2. (c) Comonomers bearing an ionic group

Comonomers containing an ionic group may serve to improve themiscibility of the polymer (A) with the polymer (B), particularly ifpolymer (B) itself bears ionically charged groups.

Preferred comonomers bearing an ionic group are of general formula (XII)

    Y.sup.2 --B.sup.9 --Q.sup.5 (XII)

where Y is an ethylenically unsaturated polymerisable group selectedfrom ##STR18## where R²⁶ is hydrogen or C₁ -C₄ alkyl; A" is --O-- or--NR²⁷ --, wherein R²⁷ is hydrogen or a C₁ -C₄ alkyl group or R²⁷ is agroup --B⁹ --Q⁵ ;

B⁹ is a valence bond, a straight or branched alkylene, oxaalkylene oroligo-oxaalkylene group;

K³ is a group --(CH₂)_(x) OC(O)--, --(CH)_(x) C(O)O--, --(CH₂)_(x)OC(O)O--, --(CH₂)_(x) NR²⁸ --, --(CH₂)_(x) NR²⁸ C(O)--, --(CH₂)_(x)C(O)NR²⁸ --, --(CH₂)_(x) NR²⁸ C(O)O--, --(CH₂)_(x) OC(O)NR²⁸ --,--(CH₂)_(x) NR²⁸ C(O)NR²⁸ -- (in which the groups R²⁸ are the same ordifferent), --(CH₂)_(x) O--, --(CH₂)_(x) SO₃ --, a valence bond(optionally in combination with B⁹) and x is from 1 to 12 and R²⁸ ishydrogen or a C₁ -C₄ alkyl group;

Q⁵ is an ionic group.

Preferred comonomers of formula (XII) are therefore those of formula(XIII) and (XIV): ##STR19## wherein:

R²⁶, A", B⁹, K³ and Q⁵ are as defined in relation to formula (XII).

Preferably in the compounds of formula (XIII) R²⁶ is hydrogen, methyl orethyl, more preferably methyl, so that the compound of formula (XIII) ispreferably an acrylic acid, methacrylic acid or ethacrylic acidderivative.

In the compounds of formula (XIV), K³ may for instance be a valencebond. Where K³ is a group then x is preferably from 1 to 6, morepreferably 1, 2 or 3 and most preferably x is 1. When K³ is a group--(CH₂)_(x) NR²⁶ --, --(CH₂)_(x) OC(O)NR²⁶ --, --(CH₂)_(x) NR²⁶ C(O)O--,--(CH₂)_(x) NR²⁶ C(O)NR²⁶ -- or --(CH₂)_(x) NR²⁶ C(O)NR²⁶ -- then R²⁶ ispreferably hydrogen, methyl or ethyl, more preferably hydrogen.

In the compounds of formula (XIV) preferably the vinyl group is para tothe group --K³ --B⁸ --Q⁴.

Preferably B⁹ is:

an alkylene group of formula --(CR²⁹ ₂)_(y) --, wherein the groups--(CR²⁹ ₂)-- are the same or different, and in each group --(CR²⁹ ₂)--the groups R²⁹ are the same or different and each group R²⁹ is hydrogenor C₁₋₄ alkyl, preferably hydrogen, and y is from 1 to 12, preferably 1to 6;

an oxaalkylene group such as alkoxyalkyl having 1 to 6 carbon atoms ineach alkyl moiety; or

an oligo-oxaalkylene group of formula --[(CR³⁰ ₂)_(yy) O]_(xx) (CR³⁰₂)_(yy) -- where the groups --(CR³⁰ ₂)-- are the same or different andin each group --(CR³⁰ ₂)-- the groups R³⁰ are the same or different andeach group R³⁰ is hydrogen or C₁₋₄ alkyl, preferably hydrogen, and yy isfrom 1 to 6, preferably 2 or 3, and xx is from 1 to 12, preferably 1 to6.

Preferred groups B⁹ include alkylene, oxaalkylene and oligo-oxaalkylenegroups of up to 12 carbon atoms.

Particular examples of the group B⁹ are --CH₂ --, --CH₂ CH₂ -- and--(CH₂)₆ --.

The group Q⁵ may be either anionic or cationic. Where the group Q⁵ isanionic it may for example be a carboxylate, sulphonate,hydrogenphosphate or phosphate group. Where the group Q⁵ is cationic itmay for example be a group --N.sup.• R³¹ ₃ in which each group R³¹ isthe same or different, and is hydrogen or alkyl of 1 to 6 carbon atomstwo of which groups R³¹ may together from a heterocyclic ring containingfrom 5 to 7 atoms, preferably hydrogen or methyl, a group N.sup.• Het,where Het is an unsaturated heterocyclic group such as pyridyl,substituted or unsubstituted by one or more alkyl groups of 1 to 4carbon atoms, or a group --P.sup.• R³² ₃ in which each group R³² is thesame or different and is hydrogen or alkyl of 1 to 6 carbons atoms, twoof which groups R³¹ may together form a heterocyclic ring containingfrom 5 to 7 atoms, preferably methyl.

Particular examples of comonomers bearing an ionic group include acrylicacid, methacrylic acid, 2-sulfoethyl methacrylate,2-methacryloyloxyethyl phosphate, p-styrene sulfonic acid,2-(methacryloyloxyethyl)trimethylammonium chloride, 3-aminopropylmethacrylamide and vinylbenzyl trimethylammonium chloride.

Comonomers containing an ionic group such as those of formula (XIII) and(XIV) are commercially available or may be prepared by conventionaltechniques using known reactions.

A.3. Diluent Comonomers

In addition to A.1. the residues of monomers containing a zwitterionic,and optionally A.2. residues of comonomers containing an alkyl(optionally substituted) hydrophobic group, reactive functional group orionic group, the polymers (A) bearing pendant zwitterionic groups maycomprise residues of a diluent comonomer.

Such diluent comonomers may be used to give the polymer physical andmechanical properties desirable for blending with the polymer (B) forexample to improve miscibility. They may be of any known conventionalradical polymerisable, preferably ethylenically unsaturated, typecompatible with other comonomer(s).

Particular examples of diluent comonomers include alkyl(alk)acrylatepreferably containing 1 to 4 carbon atoms in the alkyl group of theester moiety, such as methyl (alk)acrylate; a mono- or, usuallydi-alkylamino alkyl(alk)acrylate, preferably containing 1 to 4 carbonatoms in the or each alkyl moiety of the amine and 1 to 4 carbon atomsin the alkylene chain, e.g. 2-(dimethylamino)ethyl (alk) acrylate; and(alk) acrylamide, such as acrylamide; an alkyl- or dialkyl-(alk)acrylamide preferably containing 1 to 4 carbon atoms in the alkylgroup of the amide moiety; a hydroxyalkyl (alk)acrylate preferablycontaining from 1 to 4 carbon atoms in the hydroxyalkyl moiety, e.g. a2-hydroxyethyl (alk)acrylate; a vinyl monomer such as an N-vinyl lactam,preferably containing from 5 to 7 atoms in the lactam ring, for instancevinyl pyrrolidone, or an ester such as vinyl acetate; or styrene or astyrene derivative which for example is substituted on the phenyl ringby one or more alkyl groups containing from 1 to 6, preferably 1 to 4,carbon atoms, and/or by one or more halogen, such as fluorine atoms,e.g. (pentafluorophenyl)styrene.

Other suitable diluent comonomers include polyhydroxyl, for examplesugar, (alk)acrylates and (alk)acrylamides in which the alkyl groupcontains from 1 to 4 carbon atoms, e.g. sugar acrylates, -methacrylates,-ethacrylates, -acrylamides, -methacrylamides and -ethacrylamides.Suitable sugars include glucose and sorbitol. Particularly suitablediluent comonomers include methacryloyl glucose or sorbitolmethacrylate.

Further diluents which may be mentioned specifically includepolymerisable alkenes, preferably of 2-4 carbon atoms, eg. ethylene,dienes such as butadiene, alkylene anhydrides such as maleic anhydrideand cyano-substituted alkylenes, such as acrylonitrile.

Diluent comonomers may be obtained by conventional known methods.

Of the above diluent comonomers some are inert and act simply to modifythe physical and mechanical properties of copolymers containing them.Others, and in particular the hydroxyalkyl(alk)acrylates andpolyhydroxyl (alk)acrylates have a reactive role in addition to simplymodifying physical and mechanical properties. Such comonomers containfunctional groups, such as hydroxyl groups, which may react with acrosslinking group or may react with reactive groups in other moleculesto attach them to the copolymer.

Preparation of Polymer (A)

The polymers (A) bearing pendant zwitterionic groups formed frompolynmerisable ethylenically unsaturated groups may be prepared byconventional techniques for polymerisation, typically thermal orphotochemical polymerisation. Where comonomers capable of producingcrosslinking are present, the polymerisation conditions are set suchthat crosslinking does not occur during polymerisation. Thus, forexample, actinic radiation would not be used to prepare a polymercontaining a monomer which can form crosslinks by exposure to actinicradiation.

For thermal polymerisation a temperature from 40 to 100° C., typically50 to 80° C. is used. For photochemical polymerisation actinic radiationsuch as gamma, U.V., visible, or microwave radiation may be used.Typically U.V. radiation of wavelength 200 to 400 nm is used.

The polymerisation is generally performed in a reaction medium, which isfor instance a solution or dispersion using as a solvent for exampleacetonitrile, dimethyl formamide, chloroform, dichloromethane, ethylacetate, dimethyl sulphoxide, dioxan, benzene, toluene, tetrahydrofuran,or where the polymer does not contain groups which react with proticsolvents, water or an alkanol containing from 1 to 4 carbon atoms, e.g.methanol, ethanol or propan-2-ol. Alternatively, a mixture of any of theabove solvents may be used.

The polymerisation may be carried out in the presence of one or morepolymerisation initiators, usually free radical generators, usuallyperoxides or azo initiators, such as benzoyl peroxide,2,2'-azo-bis(2-methylpropionitrile) or benzoin methyl ether. Otherpolymerisation initiators which may be used are disclosed in "PolymerHandbook", 3rd edition, Ed. J. Brandrup and E. H. Immergut, Pub.Wiley-Interscience, New York, 1989.

Generally the polymerisation is performed for 1 to 72 hours, preferably8 to 48, for instance 16 to 24 hours, and under an inert atmosphere offor example nitrogen or argon. The polymer is generally purified bydialysis, precipitation in a non-solvent (e.g. diethyl ether or acetone)or ultrafiltration. The resulting polymer is generally dried undervacuum, eg. for 5 to 72 hours and has a molecular weight from 10,000 to10 million, preferably from 20,000 to 1 million.

The precise proportion and nature of the various comonomers used toprepare a copolymer comprising residues of a comonomer containing azwitterionic group and a further comonomer may be adjusted to provide acopolymer which is particularly suitable for blending to a particularpolymer (B). The monomer composition which is subjected topolymerisation to provide a polymer according to the invention comprisesa minimum of 0.01%, preferably 1%, more preferably 5% by weight ofmonomer or monomers containing a zwitterionic group bearing a centre ofpermanent positive charge and a maximum of 99.9%, preferably 99%, morepreferably 95% by weight of other monomer or monomers. Such othermonomer or monomers may be a monomer or monomers containing anoptionally substituted alkyl (usually hydrophobic) group, a reactivefunctional group, an ionic group or a diluent monomer or monomers.

Where the polymer (A) is a copolymer comprising residues of comonomerbearing zwitterionic groups and comonomer containing an optionallysubstituted alkyl group then preferably the comonomer compositioncomprises no more than 95%, more preferably no more than 90% and evenmore preferably no more than 80% by weight of comonomer or comonomerscontaining an alkyl group (eg hydrophobic alkyl, fluoroalkyl or siloxanegroup) the balance of the composition being comonomer or comonomerscontaining a zwitterionic group diluent monomer or monomers and/orcrosslinkable monomer or monomers (i.e. which cross-link during thepolymerisation reaction). Such a composition typically comprises up to50% by weight of diluent comonomer or comonomers. Where diluentcomonomer is present, it preferably comprises at least 1%, morepreferably 5%, by weight of the total comonomer composition. Wherepresent, crosslinkable comonomer or comonomers generally comprise from0.1% to 20% by weight of the total comonomer composition.

Preferably the molar ratio such a copolymer of comonomer residuesbearing a zwitterionic group to comonomer residues containing ahydrophobic alkyl, fluoroalkyl or siloxane group is from 5:95 to 80:20,more preferably 10:90 to 50:50. In addition the copolymer preferablycomprises from 5% to 50%, more preferably 10% to 25%, by mole residuesof diluent monomer and/or from 0.1 to 20%, more preferably 1% to 10%, bymole residues of crosslinkable comonomer, provided that where residuesof both diluent and crosslinkable comonomer are present, they do notexceed in combination 50%, preferably 35% by mole.

Where the polymer (A) is a copolymer comprising residues of a comonomerwhich comprises a reactive group or ionic group, preferably the molarratio of residues of bearing a zwitterionic group to residues containinga reactive group or ionic group is from 10:90 to 95:5, more preferably50:50 to 90:10. In addition the copolymer preferably comprises from 5%to 50%, more preferably 10% to 25%, by mole residues of diluent monomerand/or from 0.1 to 20%, more preferably 1% to 10%, by mole residues ofcrosslinkable comonomer, provided that where residues of both diluentand crosslinkable comonomer are present, they do not exceed incombination 50%, preferably 35% by mole.

In addition the monomer or comonomer composition may comprise furthercomponents such as a polymerisation initiator, chain transfer agent,acid, base, surfactant, emulsifier or catalyst of conventional type eachin an amount from 0.1% to 5%, typically from 0.2% to 3% and preferablyabout 0.5%, by weight each relative to the total weight of the monomers.

(B) Polymers having desirable physical and/or mechanical properties

According to the present invention, the polymer (A) containing pendantzwitterionic groups is blended with a polymer (B) having desirablephysical and/or mechanical properties. Such a polymer may be athermoplastic, elastomer or thermosetting material. Preferably, thepolymer (B) is a thermoplastic such as a polyolefin, polyvinylchloride(PVC), poly(alk)acrylate, such as methyl methacrylate, polyurethane, orfluorinated polyolefin.

In particular, the polymer (B) may be a polymer or copolymer, or amixture of polymers or copolymers, which is already known for use in aparticular application, such as a biomedical application. Table 1 belowlists known polymers with biomedical applications which may be used inthe blends of the present invention:

                          TABLE 1                                             

    ______________________________________                                        POLYMER             USES                                                      ______________________________________                                        Acrylate elastomers.                                                                              Prostheses                                                  Chlorosulfonated polyethylene       Vascular surfaces                         (Hypalon).                                                                    Pure natural rubber.                                                          Polyurethanes (Esthane) (Ostamer)   Prostheses, artif icial                   (Biomer) (Pellethane) (Lycra/       hearts, vascular                          Spandex) (Cardiothane) (Tecoflex). surfaces.                                  Silicone rubber (Silastic).         Artificial hearts and                                              valves, blood oxygenator                                                     films, shunts.                                        Cellophane.                         Dialysis membranes.                       Cellulose acetate.                                                            Fluorocarbons (Teflon) (PVDC)      Vascular and bulk                          (FEP) (PVOF)          implants.                                               Polysulfones                        Separation Membranes.                     Polyhydroxyethylmethacrylate        Contact lenses, drug                      (PHEMA).                            deliver, catheters,                       Polymethylmethacrylate (PMMA)      suture coatings,                           (Lucite) (Plexiglas) (Perspex).     prostheses, wound care                    Polyethylmethacrylate (PEMA).       dressings.                                Polyamides (Nylon) (Dacron).        Sutures, fabrics.                         Polyethyleneterephthalate                                                     (Terylene) (Mylar)                                                            Silk.                                                                         Polymonochloro-p-xylene.            Encapsulants of                           Epoxy resins.                       electronic components                                                           for implantation.                       Polyethylene (Vitrathene).          Prostheses, tubing.                       Polypropylene.                      Cornponents of blood                      Polycarbonates                      oxygenators and                           Polystyrene                         dialyzers, heart valves.                  Polyvinylalcohol.                   Dialysis films.                           Polyvinylchloride (PVC).            Blood bags, blood                         Vinylchloride copolymers            tubing, prostheses.                       Polyvinylidenechoride.              Vascular surfaces.                      ______________________________________                                    

Generally the blends of the present invention will contain from 1 to 90%by weight of polymer (A) containing pendant zwitterionic groups and from99 to 10% of polymer (B) having desirable physical and/or mechanicalproperties. The precise proportions of the polymers (A) and (B) willdepend upon the compatibility of the two polymers for blending and, itmay be necessary to test the polymers together for their compatibility.This may be achieved by blending different proportions of the polymers(A) and (B) to obtain a blend with the desired balance of mechanical andphysical properties as well as biocompatibility. In particular, theproportions of the two polymers may be adjusted so as to obtain desiredimpact resistance, tensile strength, flexural modulus, low temperaturebrittleness, friction co-efficient, film permeability, film tearresistance, film shrinkage, surface and volume resistivity, surfacewettability and/or contact angle.

The minimum quantity of polymer (A) will depend upon the particularpolymer (B), the content of zwitterionic groups in the polymer (A) andthe desired use of the blend. However, the content of polymer (A) shouldbe sufficient to provide a detectable modification to the biocompatibleproperties of the blend compared to the unblended polymer (B).Preferably the blend will contain at least 1%, more preferably 10% andstill more preferably 30% of polymer (A). The improvement in each of thefibrinogen absorption and the platelet activation should be so as toachieve a value of less than 80%, more preferably less than 60% of thevalue of polymer B alone.

It is believed the improved biocompatibility is due in part to increasedhydrophilicity compared to the base polymer. Another property whichimproves and which may also be due in part to increased hydrophilicityis lubricity i.e. a reduced co-efficient of friction. The improvedwettability due to increased hydrophilicity (which can be observed bydetermining the contact angle of water on the surface) may allow waterto act as a wetting lubricant to a greater extent due to thezwitterionic groups. This may be a desirable property, for instancewhere a product is required to slide easily in contact with othersurfaces, eg within the body, minimal modification to the biocompatibleproperties may be tolerated in the invention if accompanied by increasedlubricity especially where a product is in contact with the body for ashort time only, eg catheters and the like.

This increased lubricity forms the basis for a further invention inwhich the coefficient of friction in the presence of aqueous liquid ofthe surface of an article is reduced by the provision of boundzwitterionic groups.

In this invention the zwitterionic groups may be any of those defined bygroup X above. The zwitterionic group is bound at the surface such thatit is not removed by aqueous liquid in contact with the surface and sois usually covalently bound to polymer which forms the surface or is onthe surface and which is water-insoluble. In some circumstances it maybe possible for the zwitterionic group to be a part of a polymer whichis itself water-soluble but is bound to a substrate surface so that itcannot be removed by water eg by being bound by strong ionic bonds or byhydrogen-bonding interaction.

In the preferred embodiment of the invention the zwitterionic groups areintroduced at the surface of the article as pendant groups on a polymerA which is blended with a polymer B having suitable physical and/ormechanical properties and the blend of the polymers is then used to formthe article, for instance by shaping as described above. However it isalternatively possible to introduce the zwitterrionic groups by coatinga polymer containing such groups on to the surface of a preformedarticle. The polymer may, after coating, be bound to the article byhydrogen-bonding interactions, by chemical reaction to provide acovalent bond with the underlying polymer surface or by counterionicattraction between oppositely charged ionic groups on the coatingpolymer and on the coated surface. Products of this type are describedin our earlier application (not published at the priority date of thefirst invention herein) WO-A-9301221.

Other ways of providing articles having zwitterionic groups at thesurface where the article is formed of a reactive, usually polymericmaterial are by chemical reaction of a preformed article with a reagentwhich comprises the zwitterionic group and a chemically reactive groupwhich is suitable for reaction with the material at the surface. Variousderivatisation reactions of this type are described in our earlierapplications EP-A-0032622, EP-A-0157469, WO-A-9113639 and WO-A-9305081.A further way of incorporating the zwitterionic group is to form apolmer from monomers including at least one monomer which has azwitterionic group. Such monomers may be for formation of polyesters,for instance as described in our earlier publication EP-A-0275293, forformation of polyurethanes, for instance as described in EP-A-0199790,or for formation of addition polymers from ethylenically unsaturatedmonomers for instance as described in WO-A-9207885.

The utility of this invention is primarily in the medical field, forinstance for any instrument which is required to slide against any othersurface in the presence of aqueous liquid, usually body fluids. Suchinstruments are for instance catheters, guide wires, endoscopes,instruments used in keyhole surgery, ostomy connectors or otherpermanent ports, dilators of various types, contact lenses, etc. Theincreased lubricity can be demonstrated qualitatively by observing theslipperiness of the article in the presence of water or other aqueousliquid. The coefficient of friction measured by routine techniques canbe used to give a quantitative measurement of the increased lubricity,for instance as compared to the article formed in the absence of thezwitterionic groups or polymer containing the zwitterionic groups.

In addition, the blends of the present invention may further compriseconventional additives used in polymeric materials such as plasticisers,fillers, colourants, UV absorbers, anti-oxidants and/or preservatives,such as biocides, which may be included in conventional amounts so as tobe compatible with the polymers present in the blend.

The present invention further provides a process for producing a blendof the present invention, which comprises blending a preformed polymer(A) bearing zwitterionic pendant groups and a polymer (B) havingdesirable mechanical and/or physical properties.

Such blending may be carried out by conventional techniques for blendingsolid or liquid polymeric materials, including known solid statephysical mixing techniques such as roll-milling, Banbury mixing, screwextrusion and disk compounding. Alternatively, blending may be carriedout using aqueous dispersions and/or solutions of the polymers (A) and(B) or dispersions and/or solutions of the polymers (A) and (B) in anorganic solvent and the water and/or solvent removed for instance byevaporation. or by precipitation of polymer followed by liquid/solidseparation as normal. Such blending may be carried out usingconventional liquid phase blending techniques such as high or low shearmixers. These techniques are used as for known polymer blendingoperations. Using routine procedures suitable mixing conditions andchoice of ingredients can be selected to obtain a blend having thedesired homogeneity. Crosslinking or other chemical reaction may takeplace during mixing, as is known in the blending art.

Where the polymer (B) is a thermoset polymer, blending by such mixingtechniques may not be possible. In such circumstances, it may thereforebe necessary to include the polymer (A) in a blend with the monomers ofthe polymer (B) or a pre-polymer of polymer (B) prior to final polymerformation eg cross-linking to form the thermoset material. Clearly, insuch circumstances, polymer (A) must be able to withstand thepolymerisation conditions and/or cross-linking conditions for polymer(B) without adverse effects. Where the polymer (A) also includesreactive or cross-linkable groups, then these may take part in thethermosetting reaction or crosslink to the polymer (B) to modify theproperties of the final blended polymer.

The invention further provides a shaped article formed from a polymericblend according to the present invention. Such articles may be formed ina conventional manner, for example by extrusion or injection moulding orother moulding techniques and/or by machining as necessary for thedesired end shape appropriate to the nature of the particular materialin question, for instance for the uses mentioned in table 1 above, inwhich the surface of the article is in contact with a biological liquid.Usually a protein- or cell-containing liquid, such as blood, plasma,serum or tear film.

In particular, the blends of the present invention are suitable for usein surgical implants or prostheses, bioseparation apparatus, bloodcarrier bags, dialysis membranes, blood oxygenator films, tubing for usein prostheses, in extra corporeal circuitry or in catheters, connectors,stoppers, closures for diagnostic catheters, surgical drapes and tapes,and encapsulants for bio-medical applications. In addition, they aresuitable for use as casings for electronic devices, as contact lenses,intraocular lenses and other ophthalmic implants and cell culturematerials.

The blends of the present invention are preferred to graft polymers withzwitterionic groups formed according to WO-A-9305081 as they allow for awider range of base; polymers A and B to be used and, since the polymerscan bet purified to remove unreacted monomer or low molecular weightoligomer before blending with ease, provide products without problems ofcontamination by low molecular weight impurities.

The present invention will now be illustrated by the following Examples:

EXAMPLES

The following assays have been used to evaluate the blends according tothe present invention:

Water Content

A sample of the blend is soaked in deionised water, removed whenequilibrium is reached, excess surface water is removed, the sample isweighed, dried under vacuum until there is no further weight change (egat a raised temperature in the range 60 to 120° C. as appropriate) andreweighed.

Protein adsorption using an enzyme immunoassay

The assay determines absorption of human fibrinogen, a components ofblood serum, at a surface. This protein is representative of proteinwhich is typically adsorbed at a surface in contact with blood. Theassay can be readily modified to determine the absorption of otherproteins.

Discs (7 mm in diameter) of untreated material (as controls) andmaterial treated with polymer as described below, were prepared andwashed with phosphate buffered saline (PBS) for at least 10 minutes inthe wells of microplates. The samples were incubated with human plasma(300 μl) for 10 minutes and then washed with PBS three times. Each ofthe test samples and each of the control samples were treated with humanfibrinogen-specific antibody (300 μl) for 30 minutes and again washedwith PBS three times. As a control for non-specific binding of antibodyto the samples, each sample was also incubated with non-specificantibody (300 μl) for 30 minutes. A conjugate of horseradish peroxidaseand a second antibody specific to the first antibody (300 μl) was addedto both the test samples and the controls and incubated for 30 minutesbefore washing. Each of the test samples and the controls weretransferred to new microplates and a solution of 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) in phosphate-citrate buffer (300μl,0.6 mg/ml) added, the reaction was allowed to proceed for 10 minutes.At this time an aliquot of the mixture (200 μl) was removed and added toa solution of citric acid and sodium azide in distilled water (20 μl,0.21 g/ml and 2 mg/ml respectively). The optical density of thesolutions was measured using a Techgen automated plate reader at 650 nmusing the ABTS solution as blank.

In an alternative procedure, rather than using ABTS, each of the sampleswas transferred to wells of new microplates and a solution ofo-phenylene diamine (OPD) in phosphate-citrate buffer (300 μl, 0.4mg/ml) added, and the reaction was allowed to proceed for 10 minutes. Atthis time an aliquot of the mixture (200 μl) was removed from each welland the optical density of the solutions was measured using a Techgenautomated plate reader at 450 nm using the OPD solution as blank.

Activated Platelet Study

Blood was collected from a healthy adult volunteer using the doublesyringe method where the first 5 ml of blood is discarded. The blood wascollected into trisodium citrate (32 g/l) in the proportion of 9 volumesto 1 volume citrate in plastic tubes. The samples were kept at roomtemperature on a spiral mixer until used.

Discs (7 mm in diameter) of untreated material as controls and materialtreated with polymers as described below were prepared and placed intothe wells of a microplate. The samples were incubated with whole freshcitrated blood (200 μl) on a rotary mixer for 30 minutes before washingin PBS four times. Platelet activation was measured by a proprietaryassay [Lindon, J. N. et al., Blood, 68, 355 (1986)].

In an alternative procedure half of the test replicates were incubatedwith citrated blood (200 μl) and the remainder were incubated withEDTA-treated blood on a phase shaker for 30 minutes before washing inPBS four times. Platelet activation was measured in a manner similar tothat described above for detection of proteins by enzyme immunoassayusing antibodies against GMP140 to detect the presence of this plateletactivation marker on the surface of biomaterials. In the presence ofEDTA, which extracts calcium from inside platelets, activation isinhibited, so that incubation with EDTA-treated blood acts as anon-specific control for activation, obviating the need for incubationin non-specific antibody.

EXAMPLE 1

Preparation of poly(2(methacryloyloxyethyl)-2'-(trimethlammonium)ethylphosphate inner salt-co-n-dodecyl methacrylate (1:2)/High DensityPolyethylene Blend

High density polyethylene resin (35 g, 0.964 g/cm, Mw=125,000,Mn=18,000), was formed into a hide on a two roll mill at 150° C.Poly(2(methacryloyloxyethyl)-2'-(trimethylammonium) ethyl phosphateinner salt-co-n-dodecyl methacrylate (1:2) (15 g) was added and themixture blended for 10 minutes. The hide was then removed, cooled toroom temperature, cut into pieces and pressed into a film (under apressure of 10 ton/ft², at 145° C., for 10 min.) betweenpolyethyleneteraphthalate backing sheets. The film was tested for itsprotein adsorption and platelet activation properties. The results arein table 2 below.

EXAMPLE 2

Preparation of poly(2(methacryloyloxyethyl)-2-(trimethylammonium)ethylphosphate inner salt-co-n-octadecyl methacrylate (1:2)/High DensityPolyethylene Blend

High density polyethylene resin (35 g, 0.964 g/cm, Mw=125,000,Mn=18,000), was formed into a hide on a two roll mill at 150° C.Poly(2(methacryloyloxyethyl)-2'-(trimethylammonium)ethyl phosphate innersalt-co-n-octadecyl methacrylate (1:2) (15 g) was added and the mixtureblended for 10 minutes. The hide was then removed, cooled to roomtemperature, cut into pieces and pressed into a film (10 ton/ft , 145°C., 10 min.) between polyethyleneterephthalate backing sheets. into afilm (10 ton/ft², 145° C., 10 min.) between polyethyleneterephthalatebacking sheets.

EXAMPLE 3

Preparation of poly(2(methacryloyloxyethyl)-2'-(trimethylammonium)ethylphosphate inner salt-co-n-dodecyl methacrylate (1:2)/Low DensityPolyethylene Blend

Low density polyethylene resin (35 g, 0.920 g/cm), was formed into ahide on a two roll mill at 150° C.Poly(2-(methacryloyloxyethyl)-2'-(trimethylammonium) ethyl phosphateinner salt-co-n-dodecyl methacrylate (1:2) (15 g) was added and themixture blended for 10 minutes. The hide was then removed, cooled toroom temperature, cut into pieces and pressed into a film (10 ton/ft²,145° C., 10 min.) between polyethyleneteraphthalate backing sheets. Thefilm was subjected to protein deposition and platelet activation testsand the results are in table 2.

                                             TABLE 2                          

    ______________________________________                                                         ASSAY RESULTS AND CONTROL                                      % reduction vs. (control) normalised to 100%                                   Example No.                                                                             Protein Adsorption                                                                            Platelet Activation                              ______________________________________                                                1                                                                              59 (non-blended HDPE)                                                                         37 (non-blended HDPE)                                  2      49 (non-blended LDPE)   52 (non-blended LDPE)                        ______________________________________                                    

EXAMPLE 4

Preparation of poly(2(methacryloyloxyethyl)-2'-(trimethylammonium)ethylphosphate inner salt-co-n-octadecyl methacrylate (1:2)/Low DensityPolyethylene Blend

Low density polyethylene resin (30 g, 0.920 g/cm), was formed into ahide on a two roll mill at 150° C. Poly(2(methacryloyloxyethyl)-2'-(trimethylammonium) ethyl phosphate innersalt-co-n-octadecyl methacrylate (1:2) (20 g) was added and the mixtureblended for 10 minutes. The hide was then removed, cooled to roomtemperature, cut into pieces and pressed into a film (10 ton/ft², 145°C., 10 min.) between polyethyleneteraphthalate backing sheets.

EXAMPLE 5

Preparation of poly(methacryloyloxyethyl)-2'-(trimethylammonium)ethylphosphate inner salt/natural rubber latex blend

REFERENCE EXAMPLE 1

Poly(methacryloyloxyethyl)-2'-(trimethylammonium)ethyl phosphate innersalt (2.00 g) was dissolved inwater (6.00 g) and to this solutionnatural rubber latex (6.00 g, 37% solids) was added with stirring. Asmall amount of coagulated material (0.10 g dry weight) was generatedand removed. The mixture was then cast on to a glass plate in a wellformed by a sheet of PTFE with the centre removed, clamped to the glasswith bulldog clips. The cast film was then cured in an oven at 140° C.for 20 minutes to remove water by evaporation. The pale browntransparent sheet was then allowed to cool to room temperature thenwashed (readily wetting) repeatedly with water to give a cream colouredopaque sheet. The sheet had a high degree of self tackiness and readilystuck to itself irreversibly. The sheet had a water content of (22%).

EXAMPLE 6

Preparation of poly(methacryloyloxyethyl)-2'-(trimethylammonium)ethylphosphate inner salt-co-methacryloyloxyethyltrimethylammonium bromide(7:3)/natural rubber latex blend

Poly(methacryloyloxyethyl)-2'-(trimethylammonium)ethyl phosphate innersalt-co-2-methacryloyloxyethyltrimethylammonium bromide (7:3) (2.5 g)was dissolved in water (7.20 g) and filtered through glass wool to give6.70 g of solution. To this solution natural rubber latex (6.00 g, 37%solids) was added with stirring. A small amount of coagulated material(0.24 g dry weight) was generated and removed. The mixture was then caston to a glass plate in a well, formed by a sheet of PTFE with the centreremoved, clamped to the glass with bulldog clips. the cast film was thencured in an oven at 140° C. for 20 minutes. The pale brown transparentsheet was then allowed to cool to room temperature then washed (readilywetting) repeatedly with water to give a highly swollen cream colouredopaque sheet. The sheet was non tacky and highly lubricious to thetouch. The sheet had a water content of 86% and showed a reduction infibrinogen adsorption, relative to the control cast natural rubber latexsheet of 51%.

EXAMPLE 7

Preparation of poly(methacryloyloxyethyl-2'-(trimethylammonium)ethylphosphate inner salt-co-3-chloro-2-hydroxypropylmethacrylate(4:1)/natural rubber latex blend

Poly(methacryloyloxyethyl)-2'-(trimethylammonium)ethyl phosphate innersalt-co-3-chloro-2-hydroxypropylmethacrylate (4:1) (2.00 g) and sodiumhydroxide (0.1178 g) were dissolved in water (6.00 g), and to thissolution natural rubber latex (6.00 g, 37% solids) was added withstirring. The mixture was then cast on to a glass plate in a well,formed by a sheet of PTFE with the centre removed, clamped to the glasswith bulldog clips. The cast film was then cured in an oven at 140° C.for 20 minutes. The pale brown transparent sheet was then allowed tocool to room temperature then washed (readily wetting) repeatedly withwater to give a cream coloured opaque sheet. The sheet was non tacky andlubricious to the touch. The sheet had a water content of 39%.

EXAMPLE 8

Preparation of poly(methacryloyloxyethyl-2'-(trimethylammonium)ethylphosphate inner salt/natural rubber latex blend

Poly(methacryloyloxyethyl)-2'-(trimethylammonium)ethyl phosphate innersalt (2.00 g) was dissolved in water (6.00 g) and to this solutionnatural rubber latex (6.00 g, 37% solids) was added with stirring. Asmall amount of coagulated material (0.10 g dry weight) was generatedand removed. The mixture was then cast on to a glass plate in a well,formed by a sheet of PTFE with the centre removed, clamped to the glasswith bulldog clips. The cast film was then cured in an oven at 140° C.for 20 minutes. The pale brown transparent sheet was then allowed tocool to room temperature then washed (readily wetting) repeatedly withwater to give a cream coloured opaque sheet. The sheet had a high degreeof self tackiness and readily stuck to itself irreversibly.

EXAMPLE 9

Preparation of poly(methacryloyloxyethyl-2'-(trimethylammonium)ethylphosphate inner salt-co-dodecylmethacrylate (1:2)/methacrylate blend

Poly(methacryloyloxyethyl)-2'-(trimethylammonium)ethyl phosphate innersalt-co-dodecylmethacrylate (1:2) (3.00 g), methylmethacrylate (7.00 g),dichloromethane (40.0 g) and methanol (1.0 g) were mixed to give adispersion. This mixture was cast on to a glass plate using two 0.5 mmthick steel spacers and a steel spreading blade. The cast film wasallowed to dry in air for 16 hours then stored in water. The sheet had awater content of 16% and showed a reduction in fibrinogen adsorption,relative to the control cast sheet of the methylmethacrylate of 41%.

EXAMPLE 10

Preparation of poly(methacryloyloxyethyl-2'-(trimethylammonium)ethylphosphate inner salt-co-dodecylmethacrylate (1:2)/polycarbonate blend

Poly(methacryloyloxyethyl)-2'-(trimethylammonium)ethyl phosphate innersalt-co-dodecylmethacrylate (1:2) (3.00 g), polycarbonate 7.00 g),dichloromethane (40.0 g) and methanol (1.0 g) were mixed to give adispersion. This mixture was cast on to a glass plate using two 0.5 mmthick steel spacers and a steel spreading blade. The cast film wasallowed to dry in air for 16 hours then stored in water. The sheet had awater content of 13%.

EXAMPLE 11

Preparation of poly(methacryloyloxyethyl-2'-(trimethylammonium)ethylphosphate inner salt-co-dodecylmethacrylate (1:2)/polystyrene blend

Poly(methacryloyloxyethyl)-2'-(trimethylammonium)ethyl phosphate innersalt-co-dodecylmethacylate (1:2) (3.00 g), polystyrene (7.00 g),dichloromethane (40.0 g) and methanol (1.0 g) were mixed to give adispersion. This mixture was cast on to a glass plate using two 0.5 mmthick steel spacers and a steel spreading blade. The cast film wasallowed to dry in air for 16 hours then stored in water. The sheet had awater content of 10% and showed a reduction of fibrinogen adsorption,relative to the control cast sheet of the polystyrene of 28%.

EXAMPLE 12

Preparation of poly(methacryloyloxyethyl-2'-(trimethylammonium)ethylphosphate inner salt-co-dodecylmethacrylate (1:2)/polysulfone blend

Poly(methacryloyloxyethyl)-2'-(trimethylammonium)ethyl phosphate innersalt-co-dodecylmethacylate (1:2) (3.00 g), polysulfone (7.00 g),dichloromethane (40.0 g) and methanol (1.0 g) were mixed to give adispersion. This mixture was cast on to a glass plate using two 0.5 mmthick steel spacers and a steel spreading blade. The cast film wasallowed to dry in air for 16 hours then stored in water. The sheet had awater content of 11%.

EXAMPLE 13

Preparation of poly(methacryloyloxyethyl-2'-(trimethylammonium)ethylphosphate inner salt-co-dodecylmethacrylate (1:2)/methylmethacrylateblend

Poly(methacryloyloxyethyl)-2'-(trimethylammonium)ethyl phosphate innersalt-co-dodecylmethacylate (1:2) (5.00 g), methylmethacrylate (5.00 g),dichloromethane (40.0 g) and methanol (1.0 g) were mixed to give adispersion. This mixture was cast on to a glass plate using two 0.5 mmthick steel spacers and a steel spreading blade. The cast film wasallowed to dry in air for 16 hours then stored in water. The sheet had awater content of 26% and showed a reduction in fibrinogen adsorption,relative to the control cast sheet of methylmethacrylate of 48%.

EXAMPLE 14

Preparation of poly(methacryloyloxyethyl-2'-(trimethylammonium)ethylphosphate inner salt-co-n-butylmethacrylate (1:2)/methylmethacrylateblend

Poly(methacryloyloxyethyl)-2'-(trimethylammonium)ethyl phosphate innersalt-co-n-butylmethacrylate (1:2) (3.62 g), methylmethacrylate (6.38 g),dichloromethane (40.0 g) and methanol (1.0 g) were mixed to give adispersion. This mixture was cast on to a glass plate using two 0.5 mmthick steel spacers and a steel spreading blade. The cast film wasallowed to dry in air for 16 hours then stored in water. The sheet had awater content of 19% and showed a reduction in fibrinogen adsorption,relative to the control cast sheet of methylmethacrylate of 64%.

EXAMPLE 15

Preparation of poly(methacryloyloxyethyl-2'-(trimethylammonium)ethylphosphate innersalt-co-dodecylmethacrylate-co-1H,1H,2H,2H-heptadecafluorodecylmethacrylate(1:1:1)/methylmethacrylate blend

Poly(methacryloyloxyethyl)-2'-(trimethylammonium)ethyl phosphate innersalt-co-dodecylmethacrylate -co-1H,1H,2H,2H-heptadecafluorodecylmethacrylate (1:1:1) (2.00 g),methylmethacrylate (8.00 g), dichloromethane (40.0 g) and methanol (1.0g) were mixed to give a dispersion. This mixture was cast on to a glassplate using two 0.5 mm thick steel spacers and a steel spreading blade.The cast film was allowed to dry in air for 16 hours then stored inwater. The sheet had a water content of 7%.

EXAMPLE 16

70:30 Solution blend of polyacrylonitrile (PAN)/polyvinylchloride (PVC)copolymer and poly(methacryloyloxyethyl)-2'-(trimethylammonium)ethylphosphate inner salt-co-alkyl methacrylate copolymers

PAN/PVC (42 g) was mixed with thepoly(methacryloyloxyethyl)-2'-(trimethylammonium)ethyl phosphate innersalt copolymer (including the comonomer mentioned in the table) (18 g)and dissolved in pyrrolidinone (660 g) at 60° C. A pale yellow solutionformed which remained clear at room temperature. Blended polymer wasisolated by dropwise addition to water (7 L) to give a precipitate. Theprecipitated polymer was washed with water (28 L) and dried in vacuo at60° C. The results are given in Table 3. TABLE 3

    __________________________________________________________________________    COPOLYMER                                                                                Ratio of Alkyl                                                        Methacrylate:                                                                 methacryloyloxyethyl)-2                                                                              '-  ELEMENTAL ANALYSIS                                Alkyl (trimethylammonium) Yield FOUND (Theoretical)                         Example                                                                            Methacrylate                                                                        ehtyl phosphate inner salt                                                                (%)                                                                              C   H  N  P                                         __________________________________________________________________________    16.1 Dodecyl                                                                             2:1         96  53.5                                                                             6.6                                                                              7.7                                                                              1.1                                                                           (55.4)  (6.7) (8.8) (1.1)                   16.2     Octedecyl               2:1              98    54.2   6.7                                              7.7   0.93                                                                                                 (56.5)                                           (6.9) (8.7) (0.96)                          16.3     Octedecyl               1:2              97    50.9   6.2                                              8.1   1.8                                                                                              (53.2)                                               (6.4) (9.2) (2.0)                         __________________________________________________________________________

EXAMPLE 17

Formation of an ultafiltration membrane from a solution blend of PAN/PVCcopolymer and poly(methacryloyloxyethyl)-2'-(trimethylammonium)ethylphosphate inner salt-co-alkyl methacrylates

Blended materials from example 16 above were dissolved in pyrrolidinoneto form solutions of between 10 and 20% weight volume. Membranes werecast on to clean glass plates at a thickness of between 100 and 200 μm(typically (150 μm). The solvent was allowed to evaporate for between 30s and 5 minutes at a relative humidity of 50% and then the membrane wasimmersed in a water bath. Asymmetric ultrafiltration membranes formedwith nominal cut-off of between 500 and 1,000,000 Daltons. The membraneshad physical properties analogous to the non-blended materials. Therewas no measurable protein adsorption on the blended materials whereasthe PAN/PVC showed considerable protein adsorption.

EXAMPLE 18

Preparation of poly(2(methacyloyloxyethyl)-2'-(trimethylammonium)ethylphosphate inner salt-co-n-dodecyl methacrylate (1:2)/Polyurethane(Tecoflex) Blend

Tecoflex (20 g), poly(2(methacryloyloxyethyl)-2'-(trimethylammonium)ethyl phosphate inner salt-co-n-dodecyl methacrylate (1:2) (1.1 g),ethyl acetate (40 g) and propan-2-ol (40 g) were mixed to give asolution, then the solvents removed on a rotary evaporator. The dryblended material was then pressed into a film (10 ton/ft², 110° C., 10min.) between polyethylene terephthalate backing sheets.

EXAMPLE 19

Preparation of poly(2(methacyloyloxyethyl)-2'-(trimethylammonium)ethylphosphate inner salt-co-n-dodecyl methacrylate (1:4)/Polyurethane(Tecoflex) Blend

Tecoflex (7.5 g), poly(2(methacryloyloxyethyl)-2'-(trimethylammonium)ethyl phosphate inner salt-co-n-dodecyl methacrylate (1:4)(2.5 g),dichloromethan (100 g) were mixed to give a solution, then the solventsremoved on a rotary evaporator. The dry blended material was thenpressed into a film (10 ton/ft², 110° C., 10 min.) between polyethyleneterephthalate backing sheets.

REFERENCE EXAMPLE 1

Preparation of 2(methacryloyloxyethyl)-2'-(trimethylammonium ethylphosphate inner salt and homopolymer thereof

The preparation is illustrated by the reaction scheme A which follows.

a) 2-Chloro-1,3-dioxaphospholane (1)

In a flask fitted with a pressure equalising dropping funnel, refluxcondenser (fitted with a CaCl₂ guard tube) and magnetic stirrer, wasplaced a solution of phosphorus trichloride (220 ml; 346.3 g; 2.52 mol)in dichloromethane (500 ml). Ethylene glycol (139 ml; 154.7 g, 2.49 mol)was then added dropwise via the dropping funnel at such a rate that theevolution of HCl did not become too excessive. On the addition of theethylene glycol, the condenser was arranged for distillation, and thedichloromethane removed at atmospheric pressure. When the distillatetemperature reached 60° C. the flask was arranged for vacuumdistillation using a water pump, Distillation then gave2-chloro-1,3-dioxaphospholane (158 ml; 224.5 g; 71.3%) as a colourlessmobile liquid (which fumes in moist air) b.pt. 36-40° C./21 mm Hg. [cf45.5-47° C./20 mm Hg, Lucas et al, J. Am. Chem. Soc., 72, 5491, (1950)].

IR (cm⁻¹, thin film) 2980, 2905, 1470, 1210, 1005, 930, 813, 770.

b) 2-Chloro-2-oxo-1,3,2-dioxaphospholane (2)

In a flask fitted with a magnetic stirrer, reflux condenser (fitted,with a CaCl₂ guard tube) and sintered glass gas inlet tube, was placed asolution of 2-chloro-1,3-2-dioxaphospholane (100.8 g; 0.797 mol) in drybenzene (200 ml). The solution was stirred and a steady stream of oxygenwas bubbled through the solution. The reaction was mildly exothermic,and temperature control was achieved by allowing the solvent to ref lux.The oxygen was passed through the reaction mixture for 6 hours. Thesolvent was removed by rotary evaporation, and the colourless mobileresidue distilled to give 2-chloro-2-oxo-1,3,2-dioxaphospholane (2)(87.41 g; 77%) as a colourless mobile liquid -b.pt 95-97° C./0.2 mbar(c.f. 102.5-105° C./1 mbar (Edmundson, Chem. Ind. (London)), 1828(1962); 79° C./0.4 mbar (Umeda et al., Makromol. Chem. Rapid Commun., 3,457, (1982)].

IR(cm⁻¹, thin film) 2990, 2910, 1475, 1370, 1310, 1220, 1030, 930, 865,830.

c) 2(2-Oxo-1,3,2-dioxaphospholan-2-yloxy)ethyl methacrylate (3)

In a flask fitted with a magnetic stirrer, low temperature thermometer,and a pressure equalising funnel fitted with a silica gel guard tube,was placed a solution of 2-hydroxyethylmethacrylate (20.00 g, 0.154 mol)and triethylamine (15.60 g; 0.154 mol) in dry diethyl ether (300 ml).The solution was stirred and cooled to between -20° C. and -30° C. Asolution of freshly distilled 2-chloro-2-oxo-1,3,2-dioxaphospholane(2)(21.9 g; 0.154 mol) in dry diethyl ether (20 ml) was then added dropwiseover 30 minutes, the temperature being held at -20° C. during theaddition. Stirring was continued at this temperature for a further 1hour and then for a further hour as the reaction mixture was allowed towarm to room temperature. The precipitated triethylamine hydrochloridewas removed by filtration, and was washed well with dry ether. The etherwas removed from the combined filtrate and washings by rotaryevaporation. The cloudy oil residue was then shaken for 5 minutes withdry diethyl ether (50 ml) to precipitate a further crop of triethylaminehydrochloride, which was again removed by filtration. Removal of theether on the rotary evaporator gave (3) (34.18 g; 94.3%) as a colourlessviscous oil.

IR (cm⁻¹, thin film) 1720, 1640, 1450, 1360, 1310, 1290, 1170, 1030,930, 850. NMR (CDCl₃ ; 60 MHz, δ ppm) 1.95 (s,3H), 4.25-4.70 (m,8H),5.70 (m,1H), 6.25 (m,1H). Rf 0.9 (SiO₂, eluting with 10% methanol:90%dichloromethane; spot visualised with molybdenum blue spray reagent andwith iodine vapour).

d) 2(Methacryloyloxyethyl)-2'-(trimethylammonium)ethyl phosphate innersalt (4).

The phospholane (3) (67.20 g; 0.285 mol) was dissolved in 100 ml of dryacetonitrile, and placed in a heavy walled tissue culture bottle. Thephospholane solution was then treated with a solution of anhydroustrimethylamine (25.74 g; 0.436 mol) in dry acetonitrile (100 ml). Thevessel was then sealed, and placed in a water bath held at 50° C. for 30hours. The vessel was opened, and the solution brought to the boil. Thesolution was filtered whilst hot, and then set aside forcrystallisation.

The product was collected by filtration, and most of the solvent removedby suction. The wet product was then washed thoroughly with anhydrousether, then dried under reduced pressure, to give (4) as a whiteamorphous, hygroscopic solid (51.16 g; 61%). Evaporation of the motherliquor gave a very viscous oil (20.00 g; 23%), from which furtherproduct (4) crystallised on standing at -20° C. TLC (silica gel plates,eluting with methanol/dichloromethane (1:1 v/v)) showed one spot Rf 0.1,which was revealed with Dragendorff's reagent, Molybdenum blue sprayreagent, and iodine vapour.

IR(cm⁻¹ 1720, 1640, 1320, 1300, 1230, 1170, 970, 750. NMR (D₂ O; 60 MHz;δ ppm) 2.0 (s,3H), 3.27 (s,9H) 3.60-4.50 (m, 8H), 5.80, (m,1H) and 6.25(m,1H). CHN Found: C, 42.98%; H, 7.88%; N, 4.42%; P, 10.51%. CHN Theory:C, 44.75%; H, 7.46%; N, 4.75%; P, 10.51%.

e) Preparation of poly(methacryloyloxyethyl)-2'-(trimethylammonium)ethyl phosphate inner salt

(Methacryloyloxyethyl)-2'-(trimethylammonium)ethyl phosphate inner salt(20 g) was dissolved in propan-2-ol-(200 ml) and the solution purgedwith nitrogen (30 minutes). 2,2'-azo-bis(2-methylpropionitrile) (0.040g) was added and the temperature raised to 60° C. The reaction solutionwas stirred under nitrogen for 40 hours then the solution allowed tocool to room temperature. The solvent was removed on a rotary evaporatorand the solid redissolved in dichloromethane/methanol (80:20) solution(100 ml). The polymer was isolated by precipitation in acetone (1.5 L)followed by vacuum filtration under a nitrogen atmosphere. The productwas then dried under vacuum at room temperature to give a yield of 18.2g (91%).

NMR (200 MHz, d, ppm, CD₃ OD)4.1-4.4(b),4.0-4.2(b),3.6-3.8(b),3.3(s),1.8-2.2(b),1.0-1.6(b),1.0-1.2(b),0.8-1.1(b)

IR(cm⁻¹, KBr disc) 3431, 2960, 1723, 1484, 1240, 117, 1088, 969, 792

REFERENCE EXAMPLE 2

Synthesis of dimethyl(2-methacroyloxyethyl)-(1(2-sulphopropyl)) ammoniumbetaine inner salt

2(Dimethylamino)ethylmethacrylate was vacuum distilled and thendissolved in 0.1M dichloromethane. To this solution was added anequimolar amount of propane sultone. The betaine slowly precipitated outof solution and was recovered by filtration and washed with colddichloromethane. The reaction is shown in Reaction Scheme B.

REFERENCE EXAMPLE 3

Preparation of 1[4(4'-vinylbenzyloxy)butane]-2"-(trimethylammonium)ethylphosphate inner salt.

The synthesis is depicted in Reaction Scheme C.4-Hydroxy-1(4'-vinylbenzyloxy)butane (5)

Butanediol (40 ml; 40.68 g; 0.452 mol) was stirred in a 100 ml roundbottomed flask, and treated portionwise with potassium butoxide (17.60g; 0.144 mol). The initial reaction was exothermic. The reaction mixturewas stirred for 1.5 hours at room temperature. The resulting cloudysolution was then treated with chloromethyl styrene (20.00 g; 0.131mol). The styrene formed an upper, pale green layer, (the colourationbeing due to the presence of inhibitor), whose color darkenedconsiderably on the addition of 18-crown-6 (0.49 g; 1.86×10⁻³ mole). Theflask was stoppered, protected from light, and stirred for 28 hours atroom temperature. The mixture was then poured into water (120 ml) andextracted with dichloromethane (4×50 ml). The combined organic extractswere dried (MgSO₄) and evaporated to give viscous yellow oil (932.7 g).This oil was distilled from a small amount of CuCl to give a productshowing some impurities on TLC. The oil was then chromatographed onsilica gel, initially eluting with dichloromethane/petrol (1:1) toremove the impurities. The product was then eluted off the column withethyl acetate/petrol (1:1). Evaporation of the solvent gave a colourlessoil, which was distilled to give the desired styrylbutyl alcohol as acolourless oil b.pt. 150-152°/0.4 mbar. Yield 18.70g; 69.2%.

NMR (60 MHz: CDCl₃) 1.55 (m4H C--CH₂ --C); 3.50 (m, 5H, 1H exch.; O--CH₂--, 0-H), 4.45 (s,2H; Ar-CH₂ --), 5.50 (dd, 2H, vinylic), 6.75 (dd,vinylic), 7.40 (m, 4H, Ar-H).

IR 3402, 2938, 2888, 1631, 1602, 1582, 1511, 1480, 1445, 1382, 1320,1116, 1063, 920, 907, 827, 801, 716 and 667 cm⁻¹

4(2-Oxo-1,2,3-dioxaphospholane-2-yloxyl-1(4'-vinylbenzyloxy)butane (6)

4-Hydroxy-1(4'-vinylbenzyloxy)butane (5) (10.03 g; 48.69 mmol) and driedtriethylamine (4.92 g, 48.69 mmol) were dissolved in dry diethyl ether(150 ml) and the resulting solution placed in a rigorously dried flask.The solution was cooled to -30° C. and2-chloro-2-oxo-1,3,2-dioxaphospholane (6.94 g; 48.69 mmol) addeddropwise over 30 minutes, the temperature being held at -30° C. Thereaction mixture was then stirred for a further 2 hours, during whichtime the temperature was allowed to rise to 10° C. The mixture wasfiltered and the precipitate washed with dry ether. The filtrate wasevaporated (20° C./21 mm) to give a cloudy oil. The residue was shakenwith 50 ml of dry ether and refiltered. Evaporation of the filtrate gavethe product as a viscous yellow oil (13.73 g; 90.4%).

TLC (eluting with 10% methanol 90% dichloromethane) showed one majorspot, which stained with acid molybdate reagent (Rf 0.61), IR (thinfilm) 3458, 2945, 2917, 2860, 1630, 1602, 1581, 1475, 1419, 1363, 1283,1103, 1032, 820, 842, 807, 800, 715, 610 and 421 cm⁻¹.

1[4(4'-Vinylbenzyloxy)butane]-2"-(trimethylammonium)ethyl phosphateinner salt (7)

Trimethylamine (2.00 g, 33.9 mmol) was distilled into a reaction vessel,and frozen with liquid nitrogen. A solution of the4(2-oxo-1,3,2-dioxaphospholane-2-yloxy)-1-(4'-vinylbenzyloxy)butane (6)(10.00 g, 32.1 mmol) in anhydrous acetonitrile (40 ml) was then added tothe reaction vessel, which was then sealed and placed in a thermostattedwater bath (50° C. for 50 hours). The reaction vessel was then cooled toroom temperature, opened, and the reaction mixture evaporated to abouthalf its original volume (21 mm pressure). The concentrated solution wasthen stirred at room temperature, whilst anhydrous ether (200 ml) wasadded dropwise to precipitate the product as a viscous oil. The mixturewas then left for several hours at -10° C. The product was collected bydecanting off the supernatent solid. TLC (eluting withmethanol/dichloromethane 1:1) showed one major spot at Rf 0.0-0.1 whichstained with both Dragendorffs reagent and acid molybdate.

REFERENCE EXAMPLE 4

Preparation of 2(acryloyloxyethyl)-2'-(trimethylammonium)ethyl phosphateinner salt

The synthesis is essentially analogous to that described in ReferenceExample 1 and uses a synthetic strategy analogous to that shown inReaction Scheme A.

(a) 2-(2-oxo-1,3,2-dioxaphospholan-2-yloxy)ethyl acrylate

2-Hydroxyethyl acrylate (11.5 ml, 0.1M) and triethylamine (14.6 ml) indry diethyl ether (250 ml) were cooled to -25° C. under nitrogen as asolution of 2-chloro-2-oxo-1,3,2-dioxaphospholane (14.3 g) in drydiethyl ether was added over 20 minutes. The mixture was stirred for afurther 1 hour at -20° C. and then allowed to warm to 10° C. over afurther hour. The precipitate was filtered, washed with ethyl acetate(100 ml) and the combined filtrate and washings evaporated under reducedpressure to give a pale yellow oil (21 g).

¹ H NMR (200 MHz) d (CD₃ CN) 6.4 (1H,dd), 6.2 (1H,dd), 5.9 (1H,dd),4.0-3.6 (8H,complex) ppm.

(b) 2-(Acryloyloxyethyl)-2'-(trimethlyammonium)ethyl phosphate, innersalt.

2-(2-Oxo-1,3,2-dioxaphospholan-2-yloxy) ethyl acrylate (21 g,0.095M) inacetonitrile (50 ml) was treated with a solution of triethylamine (12.1g) in acetonitrile (150 ml) in a pressure reactor at 50° C. for 17hours. The mixture was cooled and some of the excess triethylamineremoved by evaporation under reduced pressure.

The solid material was filtered under nitrogen, washed with acetonitrile(20 ml) and diethylether (50 ml) and then dried under reduced pressureto give a colourless solid (12.1 g, 45%).

¹ H NMR (200 MHz) d (D₂ 0) 6.45 (1H,dd,J1.2 and 17.1 Hz), 6.25(1H,dd,J1.2 and 10.25 Hz), 6.02 --(1H,dd, J1.23 and 10.25 Hz), 4.4(2H,m), 4.3 (2H, m), 4.2 (2H,m) 3.6(2H,m) and 3.2(9H,s) ppm.

REFERENCE EXAMPLE 5

Dodec-7-yn-1-yl Methacrylate

To dodec-7-yn-1-ol (25 g) in dichloromethane (60 ml) was added distilledtriethylamine (14.1 g). The mixture was cooled in an ice bath (0.5° C.)and stirred as distilled methacryloyl chloride (16.2 g) indichloromethane (50 ml) was added over 10 minutes. The temperature ofthe reaction was allowed to warm to ambient and the mixture stirred fortwo hours. Water (150 ml) was added and the organic layer was removedand successively extracted with water (2×150 ml) and saturated sodiumbicarbonate solution (2×150 ml), washed with brine (150 ml) and driedover anhydrous sodium sulphate. The solvent was removed under reducedpressure to give a pale yellow oily liquid which was distilled underreduced pressure (0.18 mBar, 106-110° C.) in the presence of copper (1)chloride to give dodec-7-yn-1-yl methacrylate, 17 g, 50% yield.

¹ H-NMR (200 MHz,d,ppm,CDCl₃): 0.90 (t,3H), 1.45 (m,10H), 1.70 (m,2H),1.95 (s,3H), 2.15 (m,6H), 4.15 (t,2H), 5.55 (s,1H), 6.10 (s,1H).

REFERENCE EXAMPLE 6

Preparation of poly(2(methacryloyloxyethyl)-2'-(trimethylammonium)ethylphosphate inner salt-co-n-dodecyl methacrylate (1:2)

2 (Methacryloyloxyethyl)-2'-(trimethylammonium) ethyl phosphate innersalt (12.06 g, 0.0409 mole) and n-dodecyl methacrylate (20.52 g, 0.0808mole) were dissolved in propan-2-ol (215 ml) and ethyl acetate (85 ml).The solution was stirred (250 rpm) at 23° C. under a stream of nitrogen(50 ml/min) for 30 minutes, 2,2'-azo-bis(2-methylpropionitrile) (0.0645g, 0.39 mmole) was added and the flow of nitrogen was reduced to 10ml/min, the reaction temperature was raised to 60° C. This temperatureand nitrogen flow rate were maintained for 40 hours.

The mixture was allowed to cool and vacuum filtered. The filtrate wasevaporated to dryness using a rotary evaporator and dissolved indichloromethane (120 ml) and methanol (10 ml). The polymer was isolatedfrom this mixture by precipitation in acetone (2500 ml), vacuumfiltration and drying. The polymer was redissolved in dichloromethane(100 ml) and methanol (30 ml) and isolated as described above.

The resulting polymer, obtained in 70-80% yield was a white powder.

NMR(200 MHz, d, ppm, CD₃ OD/CDCl₃) 4.2-4.4 (b), 3.8-4.2 (b), 3.6-3.8(b), 3.3 (s), 1.8-2.2 (b), 1.5-1.8 (b), 1.2-1.5 (s), 0.8-1.0 (s)

IR(cm⁻¹, KBr disc) 3430, 2929, 2854, 1732, 1469, 1246, 1156, 1089, 968,788.

Elemental Analysis theory C, 64.5; H, 9.9; N, 1.8; P, 3.9; actual C,59.0; H, 10.0; N, 1.8; P, 3.9;

The polymer had a relative viscosity in ethanol: chloroform (50:50) at25° C. of 1.13±0.02 (when prepared using methanol: THF as solvent) and1.26±0.02 (when prepared using propan-2-01: ethylacetate as solvent).

REFERENCE EXAMPLE 7

Preparation of poly(2(methacryloyloxyethyl)-2'-(trimethylammoniumlethylphosphate inner salt-co-n-octadecyl methacrylate (1:2)

The polymer was obtained by an analogous procedure to that described inReference Example 6 using2(methacryloyloxyethyl)-2'-(trimethylammonium)ethyl phosphate inner salt(3.0 g, 0.0102 mole) and n-octadecyl methacrylate (6.9 g, 0.0204 mole)dissolved in methanol (30 ml) and THF (70 ml).

The resulting polymer, obtained in 55% yield was a white solid.

NMR(100 MHz, d, ppm, CD₃ OD/CDCl₃) 4.2-4.4 (b), 3.8-4.2 (b), 3.6-3.8(b), 3.3 (s), 1.8-2.2 (b), 1.5-1.8 (b), 1.2-1.5 (s), 0.8-1.0 (s)

IR(cm⁻¹, KBr disc) 3430, 2929, 2854, 1732, 1469, 1246, 1156, 1089, 968,788.

The polymer had a relative viscosity in ethanol: chloroform (50.50) at25° C. of 1.26±0.02.

REFERENCE EXAMPLE 8

Preparation of poly(methacryloyloxyethyl)-2'-(trimethylammonium)ethylphosphate inner salt-co-methacryloylethyltrimethylammonium bromide (7:3)

(Methacryloyloxyethyl)-2'-(trimethylammonium)ethyl phosphate inner salt(4.5 g) and methacryloylethyltrimethylammonium bromide 75% aqueoussolution (2.0 g) were dissolved in ethanol (50 ml) and the solutionpurged with nitrogen (30 minutes). 2,2'azo-bis(2-methylpropionitrile)(0.020 g) was added and the temperature raised to 60° C. The reactionsolution was stirred under nitrogen for 24 hours then the solutionallowed to cool to room temperature. The polymer was isolated byprecipitation in acetone (500 ml) followed by vacuum filtration under anitrogen atmosphere. The product was then dried under vacuum at roomtemperature to give a yield of 4.0 g (67%).

NMR (200 MHz, d, ppm, CD₃ OD)4.2-4.4(b), 4.1-4.3(b), 4.0-4.2(b), 3.7(b),3.3(s), 1.8-2.2(b), 1.2-1.4 (b), 1.0-1.2(b),0.8-1.1(b)

IR(cm⁻¹, KBr disc) 3426, 2959, 1724, 1484, 1245, 1166, 1078, 969, 791

REFERENCE EXAMPLE 9

Preparation of poly(methacryloyloxyethyl)-2'-(trimethylammonium)ethylphosphate inner salt-co-3-chloro-2-hydroxypropylmethacrylate (4:1)

(Methacryloyloxyethyl)-2'-(trimethylammonium)ethyl phosphate inner salt(8.50 g) and 3-chloro-2-hydroxypropylmethacrylate (1.26 g) weredissolved in propan-2-ol (97.6 g) and the solution purged with nitrogen(30 minutes). 2,2'azo-bis(2-methylpropionitrile) (0.012 g) was added andthe temperature raised to 60° C. The reaction solution was stirred undernitrogen for 16 hours then ethanol was added. The solution was thenallowed to cool to room temperature and the polymer isolated byprecipitation in acetone (1.5 L) followed by vacuum filtration under anitrogen atmosphere. The crude product was dried under vacuum at roomtemperature then redissolved in ethanol (100 ml). The final product wasisolated by precipitation in ethyl acetate/acetone (80:20) solution (1.5L) followed by vacuum filtration under a nitrogen atmosphere. The solidwas dried under vacuum at room temperature to give a yield of 8.3 g(85%).

NMR (200 MHz, d, ppm, CD₃ OD)4.4-4.6(b), 4.2-4.4(b), 4.1-4.3(b),4.0-4.2(b), 3.7-3.9(b), 3.6-3.8(b), 3.3(s), 1.8-2.2(b), 1.1-1.4(b),1.0-1.2(b), 0.9-1.1(b)

IR(cm⁻¹, KBr disc) 3446, 2960, 1724, 1484, 1245, 1164, 1089, 970, 790

REFERENCE EXAMPLE 10

Preparation of Poly(methacryloyloxyethyl)-2'-(trimethylammonium)ethylphosphate inner salt-co-n-butylmethacrylate (1:2)

(Methacryloyloxyethyl)-2'-(trimethylammonium)ethyl phosphate inner salt(21.93 g) and n-butylmethacrylate (21.14 g) were dissolved in ethylacetate/propan-2-ol (28:72) solution (545 ml) and the solution purgedwith nitrogen (30 minutes). 2,2'-azo-bis(2-methylpropionitrile) (0.119g) was added and the temperature raised to 62° C. the reaction solutionwas stirred under nitrogen for 40 hours then the solution allowed tocool to 40° C. The solvent was removed on a rotary evaporator and thesolid redissolved in dichloromethane/methanol (92:8) solution (153 ml).The polymer was isolated by precipitation in diethylether (1.75 L)followed by vacuum filtration under a nitrogen atmosphere. The crudeproduct was dried under vacuum at room temperature then redissolved indichloromethane/methanol (92.:8) solution (153 ml). The final productwas isolated by precipitation in diethylether (1.75 L) followed byvacuum filtration under a nitrogen atmosphere. The solid was dried undervacuum at room temperature to give a yield of 31.2 g (72%).

NMR (200 MHz, d, ppm, CD₃ OD)4.2-4.4(b), 4.0-4.2(b), 3.9-4.1(b),3.6-3.8(b), 3.3(s), 1.7-2.0(b), 1.6-1.8(b), 1.4-1.6(b), 0.8-1.2(s)

IR(cm⁻¹, KBr disc) 3436, 2961, 1728, 1489, 1244, 1165, 1088, 959, 793

Elemental Analysis theory C,55.97; H,8.71; N,2.42; actual C,51.95;H,8.41; N,2.65;

REFERENCE EXAMPLE 11

Preparation of poly(methacryloyloxyethyl)-2'-(trimethylammonium)ethylphosphate inner salt-co-dodecylmethacrylate-co-1H, 1H, 2H,2H-hertadecafluorodecylmethacrylate (1:1:1)

(Methacryloyloxyethyl)-2'-(trimethylammonium)ethyl phosphate inner salt(7.23 g), dodecylmethacrylate (2.35 g) and1H,1H,2H,2H-heptadecafluorodecylmethacrylate (4.92 g) were dissolved inethyl acetate/propan-2-ol (50:50) solution (100 ml) and the solutionpurged with nitrogen (30 minutes). 2,2'azo-bis(2-methylpropionitrile)(0.016 g) was added and the temperature raised to 60° C. The reactionsolution was stirred under nitrogen for 40 hours then the solutionallowed to cool to room temperature. The solvent was removed on a rotaryevaporator and the solid redissolved in dichloromethane (30 ml). Thepolymer was isolated by precipitation in acetone (1.5 L) followed byvacuum filtration under a nitrogen atmosphere. The product was thendried under vacuum at room temperature to give a yield of 8.3 g (83%).

REFERENCE EXAMPLE 12

Preparation of natural rubber latex sheet

Natural rubber latex (6.00 g, 37% soids) was added to water (6.00 g)with stirring. The mixture was then cast on to a glass plate in a wellformed by a sheet of PTFE with the centre removed clamped to the glasswith bulldog clips. The cast film was then cured in an oven at 140° C.for 20 minutes. The pale brown transparent sheet was then allowed tocool to room temperature then washed repeatedly with water (wettingpoorly) to give a cream coloured opaque sheet. The sheet had a highdegree of self tackiness and readily stuck to itself irreversibly.##STR20## Step (a) to (d) correspond with the steps in Reference Example1 ##STR21##

We claim:
 1. A method of improving the biocompatibility of a polymer,comprising the steps of: (1) providing a polymer having desirablemechanical and/or physical properties in solution or dispersion in aliquid vehicle to provide a liquid polymer composition;(2) dispersing ordissolving into the liquid polymer composition a zwitterionic polymerbearing zwitterionic pendant groups to produce a liquid blendedcomposition; wherein the zwitterionic polymer is formed from a radicalpolymerisable monomer including zwitterionic monomer of formula (I)

    Y--B--X                                                    (I)

wherein B is a straight or branched alkylene, an oxaalkylene or anoligo-oxaalkylene chain optionally containing one or more fluorine atomsup to and including perfluorinated chains, or, if X contains acarbon-carbon chain between B and the zwitterionic moiety or if Ycontains a terminal carbon bonded to B, a valence bond; X is azwitterionic group, Y is an ethylenically unsaturated polymerisablegroup selected from ##STR22## wherein: R is hydrogen or a C₁ -C₄ alkylgroup; A is --O-- or --NR'-- where R¹ is hydrogen or a C₁ -C₄ alkylgroup or R¹ is --B--X where B and X are as defined above; and K isselected from the group consisting of:--(CH₂)_(p) OC(O)--, --(CH₂)_(p)C(O)--, --(CH₂)_(p) OC(O)O--, --O(CH₂)_(p) NR² --, --(CH₂)_(p) NR²C(O)--, --(CH₂)_(p) C(O)NR² --, --(CH₂)NR² C(O)O--, --(CH₂)_(p) OC(O)NR²--, --(CH₂)_(p) NR² C(O)NR² -- (in which the R² groups are the same ordifferent), --(CH₂)_(p) O--, --(CH₂)_(p) SO₃ --, and optionally incombination with B, a valence bond, and p is from 1 to 12 and R² ishydrogen or a C₁ -C₄ alkl group; provided that the cationic moiety ofthe zwitterionic group is located at a distant end of the pendant Xgroup from the B group; and (3) optionally in addition dispersing ordissolving into the liquid polymer composition or into the liquidblended composition at least one additive selected from the groupconsisting of plasticisers, fillers, colourants, UV absorbers,antioxidants and preservatives, said additives being biocompatible and(4) removing the liquid vehicle from the liquid blended composition ofstep (2) or step (3) to provide a solid blend.
 2. A method according toclaim 1 in which the polymer having desirable mechanical and/or physicalproperties is less hydrophilic than the zwitterionic polymer.
 3. Amethod according to claim 1 in which the polymer having desirablemechanical and/or physical properties is thermoplastic and/orelastomeric.
 4. A method according to claim 1 in which the polymerhaving desirable mechanical and/or physical properties is selected fromthe group consisting of polyolefins, vinyl halide polymers, (alk)acrylate polymers, polyurethanes, natural rubbers and synthetic rubbers.5. A method according to claim 1 in which, in the zwitterionic polymer,X is a zwitterionic group in which the anionic moiety is a phosphategroup.
 6. A method according to claim 1 in which in group X the cationicmoiety is a quaternary ammonium group.
 7. A method according to claim 5in which X is a zwitterionic group in which the cationic moiety is aquaternary ammonium group.
 8. A method according to claim 1 in which thezwitterionic monomer is of the formula ##STR23## in which R is hydrogen,methyl, or ethyl, A is --O-- or --NR¹ -- where R¹ is hydrogen or a C₁-C₄ alkyl group or R¹ is --B--X,B is a straight or branched alkylene, anoxaalkylene or an oligo-oxaalkylene chain optionally containing one ormore fluorine atoms ul, to an including perfluorinated chains, and X isa zwitterionic group in which the anionic moiety is a phosphate group.9. A method according to claim 8 in which R is methyl.
 10. A methodaccording to claim 1 in which X is selected from groups of formulae,(IVB), (IVC), (IVD) and (IVE): ##STR24## where the R⁷ groups are thesame or different and each is hydrogen or a C₁₋₄ alkyl group, and e isfrom 1 to 4; ##STR25## wherein the R⁸ groups are the same or differentand each is hydrogen or C₁₋₄ alkyl group, R^(8a) is hydrogen or a group--C(O)B¹ R^(8b) where R^(8b) is hydrogen or methyl, B¹ is a valence bondor a straight or branched alkylene, an oxaalkylene or anoligo-oxaalkylene group, and f is from 1 to 4; and if B is other than avalence bond z is 1 and if B is a valence bond z is 0, if X is directlybonded to an oxygen or nitrogen atom and otherwise z is 1; ##STR26##wherein the R⁹ groups are the same or different and each is hydrogen ora C₁ -C₄ alkyl group, R^(9a) is a hydrogen or a group --C(O)B² R^(9b)where R^(9b) is hydrogen or methyl, B² is a valence bond or a straightor branched alkylene, an oxaalkylene or an oligo-oxaalkylene group, andg is from 1 to 4; andif B is other than a valence bond z is 1 and, if Bis a valence bond z is 0 if X is directly bonded to an oxygen ornitrogen atom and otherwise z is 1; and ##STR27## wherein the R¹⁰ groupsare the same or different and each is hydrogen or a C₁₋₄ alkyl group,R^(10a) is hydrogen or a group --C(O)B³ R^(10b) where R^(10b) ishydrogen or methyl, B³ is a valence bond or a straight or branchedalkylene, an oxaalkylene or an oligo-oxaalkylene group, and h is from 1to 4; and if B is other than a valence bond z is 1 and if B is a valencebond z is 0 if X is directly bonded to the oxygen or nitrogen andotherwise z is
 1. 11. A method according to claim 10 in which X is agroup of the formula IVB in which R⁷ groups are all the same and are allmethyl.
 12. A method according to claim 1 in which the zwitterionicpolymer is formed from monomers including a comonomer of the formula IX

    Y.sup.1 Q.sup.1                                            (IX)

where Y¹ is an ethylenically unsaturated polymerisable group selectedfrom ##STR28## where R¹⁹ is hydrogen or a C₁ -C₄ alkyl group K² isselected from the group consisting of: --(CH₂)_(q) OC(O)--, --(CH₂)_(q)C(O)O, --(CH₂)_(q) OC(O)O, --(CH₂)_(q) NR²⁰ --, --(CH₂)_(q) NR²⁰ C(O)--,--(CH₂)_(q) C(O)NR²⁰ --, --(CH₂)_(q) NR²⁰ C(O)O--, --(CH₂)_(q)OC(O)NR²⁰, --(CH₂)_(q) NR²⁰ C(O)NR²⁰ -- (in which the groups R²⁰ are thesame or different), --(CH₂)_(q) O--, --(CH₂)_(q) O--, --(CH₂)_(q) SO₃--, and a valence bond and q is from 1 to 12 and R²⁰ is hydrogen or a C₁-C₄ alkyl group; and Q¹ is a reactive group capable of reacting toprovide crosslinking within the polymer having desirable physical and/ormechanical properties or to the zwitterionic polymer and/or providing areactive group on the surface of the blend.
 13. A method according toclaim 12 in which the comonomer is a compound of formula ##STR29##wherein: Q² is hydrogen, --OH or a group of the formula:

    --T--B.sup.7 --Q.sup.3

where T is --O--, or --NR²¹ -- where R²¹ is hydrogen, C₁ C₄ alkyl or agroup --B⁷ --Q³ ; wherein B⁷ is a valence bond or a straight or branchedalkylene, an oxaalkylene or an oligo-oxaalkylene chain; and Q³ is areactive group selected from the group consisting of:i) an aldehydegroup, ii) silane and siloxane groups containing one or more reactivesubstituents selected from the group consisting of a halogen or analkoxy containing from 1 to 4 carbon atoms, iii) a hydroxyl group, iv)an amino group, v) a carboxyl group, vi) an epoxy group, vii) --CHOHCH₂Hal, in which Hal is a halogen atom, viii) a succinimido group, ix)sulphonic acid ester groups, x) an imidazole carbonyl-amino group andxi) optionally substituted triazine groups.
 14. A method according toclaim 13 in which B⁷ is selected from --CH₂ --, --CH₂ CH₂ -- and--(CH₂)₆ --.
 15. A method according to claim 1 in which the zwitterionicpolymer is formed from monomers further including a compound of theformula XII

    Y.sup.2 --B.sup.9 --Q.sup.5                                (XII)

where Y² is an ethylenically unsaturated polymerisable group selectedfrom ##STR30## where R²⁶ is hydrogen or a C₁ -C₄ alkyl group; A" is--O-- or --NR²⁷ --, wherein R²⁷ is hydrogen or a C₁ -C₄ alkyl group or a--B⁹ --Q⁵ group; B⁹ is a valence bond, a straight or branched alkylene,an oxaalkylene or an oligo-oxaalkylene group; K³ is selected from thegroup consisting of:--(CH₂)_(x) OC(O)--, --(CH₂)_(x) C(O)O--,--(CH₂)_(x) OC(O)O--, --(CH₂)_(x) NR²⁸ --, --(CH₂)_(x) NR²⁸ C(O)--,--(CH₂)_(x) CONR²⁸ --, --(CH₂)_(x) NR²⁰ C(O)O--, --(CH₂)_(x) OC(O)NR²⁸--, --(CH₂)_(x) NR²⁸ C(O)NR²⁸ -- (in which the groups R²⁸ are the sameor different), --(CH₂)_(x) O--, --(CH₂)_(x) SO₃ --, and a valence bond(optionally in combination with B⁹) and x is from 1 to 12 and R²⁸ ishydrogen or a C₁ -C₄ alkyl group; and, Q⁵ is an ionic group.
 16. Amethod according to claim 1 in which the zwitterionic polymer is formedfrom monomers including a compound selected from the group consisting ofacrylic acid, methacrylic acid, 2-sulphoethyl methacrylate,2-methacryloyloxyethyl phosphate, p-styrene sulphonic acid,2-(methacryloyloxyethyl) trimethyl ammonium chloride, 3-aminopropylmethacrylamide and vinyl benzyl trimethyl ammonium chloride.
 17. Amethod according to claim 1 in which the zwitterionic polymer is formedfrom monomers including a diluent comonomer selected from the groupconsisting of alkyl (alk)acrylates containing 1 to 4 carbon atoms in thealkyl group, mono-and di-alkyl amino alkyl (alk)acrylates containing 1to 4 carbon atoms in each alkyl moiety; (alk)acrylamides; mono- ordi-alkyl (alk)acrylamides containing 1 to 4 carbon atoms in the alkylgroups; hydroxyalkyl (alk)acrylates containing 1 to 4 carbon atoms inthe hydroxyalkyl group; N-vinyl lactam containing from 4 to 7 atoms inthe lactam ring; vinyl acetate; styrene; a styrene compound substitutedby one or more alkyl groups containing 1 to 6 carbon atoms and/or by oneor more halogen atoms; polyhydroxyl (alk)acrylatesand--(alk)acrylamides; C₂₋₄ -alkenes; butadiene; maleic anhydride andacrylonitrile.
 18. A method according to claim 1 in which thezwitterionic polymer is included in an amount sufficient to reducefibrinogen adsorption and/or platelet activation performance of thepolymer having desirable physical and/or mechanical characteristics toless than 80% of the fibrinogen adsorption and/or platelet activationperformance respectively of that polymer alone, wherein the methodcomprises contacting the solid blend produced in step (4) with afibrinogen or platelet-containing liquid.
 19. A method according toclaim 1 in which the amount of the zwitterionic polymer in the liquidblend is in the range of 1 to 90% by weight, based on the total weightof zwitterionic polymer and polymers having desirable mechanical and/orphysical properties.
 20. A method according to claim 1 in which theliquid blend is coated onto a solid substrate before the liquid vehicleis evaporated, whereby a coating of the solid blend is formed on thesubstrate.
 21. A process for producing a blend, comprising the steps of:providing a preformed polymer (A) bearing zwitterionic pendant groupsand a polymer (B) having desirable mechanical and/or physicalproperties, wherein polymer (A) is more hydrophilic than polymer (B) andpolymer (A) and polymer (B) are both in solid particulate form; andblending polymer (A) and polymer (B) by a technique selected fromroll-milling, Banbury mixing, screw extrusion and disk compounding, toform a polymer (A)/polymer (B) blend, the blend having a superiorbiocompatibility than polymer (B) alone,wherein the zwitterionic polymeris formed from a radical polymerisable monomer including zwitterionicmonomer of formula (I)

    Y--B--X                                                    (I)

wherein B is a straight or branched alkylene, an oxaalkylene or anoligo-oxaalkylene chain optionally containing one or more fluorine atomsup to and including perfluorinated chains, or, if X contains acarbon-carbon chain between B and the zwitterionic moiety or if Ycontains a terminal carbon bonded to B, a valence bond; X is azwitterionic group, Y is an ethylenically unsaturated polymerisablegroup selected from ##STR31## wherein: R is hydrogen or a C₁ -C₄ alkylgroup; A is --O-- or --NR¹ -- where R¹ is hydrogen or a C₁ -C₄ alkylgroup or R¹ is --B--X where B and X are as defined above; and K isselected from the group consisting of:--(CH₂)_(p) OC(O)--, --(CH₂)_(p)C(O)--, --(CH₂)_(p) OC(O)O--, --O(CH₂)_(p) NR² --, --(CH₂)_(p) NR²C(O)--, --(CH₂)_(p) C(O)NR² --, --(CH₂)NR² C(O)O--, --(CH₂)_(p) OC(O)NR²--, --(CH₂)_(p) NR² C(O)NR² -- (in which the R² groups are the same ordifferent), --(CH₂)_(p) O--, --(CH₂)_(p) SO₃ --, and optionally incombination with B, a valence bond and p is from 1 to 12 and R² ishydrogen or a C₁ -C₄ alkyl group; and wherein, in the zwitterionicpolymer, X is a zwitterionic group in which the anionic moiety is aphosphate group.
 22. A method of using a polymer bearing zwitterionicpendant groups to increase lubricity in the presence of an aqueousliquid of a polymer having desirable physical and/or mechanicalproperties, comprising the steps of:blending a preformed polymer (A)bearing zwitterionic pendant groups with a polymer (B) having desirablephysical and/or mechanical properties, wherein the zwitterionic polymeris formed from a radical polymerisable monomer including zwitterionicmonomer of formula (I)

    Y--B--X                                                    (I)

wherein B is a straight or branched alkylene, an oxaalkylene or anoligo-oxaalkylene chain optionally containing one or more fluorine atomsup to and including perfluorinated chains, or if X contains acarbon-carbon chain between B and the zwitterionic moiety or if Ycontains a terminal carbon bonded to B, a valence bond; X is azwitterionic group, Y is an ethylenically unsaturated polymerisablegroup selected from ##STR32## wherein: R is hydrogen or a C₁ -C₄ alkylgroup; A is --O-- or --NR¹ -- where R¹ is hydrogen or a C₁ -C₄ alkylgroup or R¹ is --B--X where B and X are as defined above; and K isselected from the group consisting of:--(CH₂)_(p) OC(O)--, --(CH₂)_(p)C(O)--, --(CH₂)_(p) OC(O)O--, --O(CH₂)_(p) NR² --, --(CH₂)_(p) NR²C(O)--, --(CH₂)_(p) C(O)NR² --, --(CH₂)NR² C(O)O--, --(CH₂)_(p) OC(O)NR²--, --(CH₂)_(p) NR² C(O)NR² -- (in which the R² groups are the same ordifferent), --(CH₂)_(p) O--, --(CH₂)_(p) SO₃ --, and optionally incombination with B, a valence bond and p is from 1 to 12 and R² ishydrogen or a C₁ -C₄ alkyl group; and wherein, in the zwitterionicpolymer, X is a zwitterionic group in which the anionic moiety is aphosphate group and shaping the blend to form an article.
 23. A methodof improving biocompatibility of a polymer, comprising the steps of:(i)providing a polymer having desirable mechanical and/or physicalproperties; (ii) blending the polymer of step (I) with a polymer bearingzwitterionic pendant groups and which is more hydrophilic than thepolymer of step (I), wherein the zwitterionic polymer is formed from aradical polymerisable monomer including zwitterionic monomer of formula(I)

    Y--B--X                                                    (I)

wherein B is a straight or branched alkylene, an oxaalkylene or anoligo-oxaalkylene chain optionally containing one or more fluorine atomsup to and including perfluorinated chains, or if X contains acarbon-carbon chain between B and the zwitterionic moiety or if Ycontains a terminal carbon bonded to B, a valence bond; X is azwitterionic group, Y is an ethylenically unsaturated polymerisablegroup selected from ##STR33## wherein: R is hydrogen or a C₁ -C₄ alkylgroup; A is --O-- or --NR¹ -- where R¹ is hydrogen or a C₁ -C₄ alkylgroup or R¹ is --B--X where B and X are as defined above; and K isselected from the group consisting of:--(CH₂)_(p) OC(O)--, --(CH₂)_(p)C(O)--, --(CH₂)_(p) OC(O)O--, --O(CH₂)_(p) NR² --, --(CH₂)_(p) NR²C(O)--, --(CH₂)_(p) C(O)NR² --, --(CH₂)NR² C(O)O--, --(CH₂)_(p) OC(O)NR²--, --(CH₂)_(p) NR² C(O)NR² -- (in which the R² groups are the same ordifferent), --(CH₂)_(p) O--, --(CH₂)_(p) SO₃ --, and optionally incombination with B, a valence bond and p is from 1 to 12 and R² ishydrogren or a C₁ -C₄ alkyl group; and wherein, in the zwitterionicpolymer, X is a zwitterionic group in which the anionic moiety is aphosphate group.
 24. A method of improving the biocompatibility of apolymer, comprising the steps of:(1) providing a polymer B havingdesirable mechanical and/or physical properties in solution ordispersion in a liquid vehicle to provide a liquid polymer composition;(2) dispersing or dissolving into the liquid polymer composition azwitterionic polymer A bearing zwitterionic pendant groups to produce aliquid blended composition; (3) optionally in addition dispersing ordissolving into the said liquid polymer composition or into said liquidblended composition at least one additive selected from the groupconsisting of plasticisers, tillers, colourants, UV absorbers,antioxidants and preservatives, said additives being biocompatible; and(4) removing the liquid vehicle from the liquid blended composition ofsteps (2) or step (3) to provide a solid blend; in which thezwitterionic polymer A is formed from radical polymerisable monomersincluding at least 5 mole % zwitterionic monomer of formula (I)

    Y--B--X                                                    (I)

wherein B is a straight or branched alkylene, an oxaalkylene or anoligo-oxaalkylene chain optionally containing one or more fluorine atomsup to and including perfluorinated chains, or if X contains acarbon-carbon chain between B and the zwitterionic moiety or if Ycontains a terminal carbon bonded to B, a valence bond; X is azwitterionic group, Y is an ethylenically unsaturated polymerisablegroup selected from ##STR34## wherein: R is hydrogen or a C₁ -C₄ alkyl;A is --O-- or --NR¹ is a hydrogen or a C₁ -C₄ alkyl group or R¹ is--B--X where B and X are as defined above; and K is selected from thegroup consisting of:--(CH₂)_(p) OC(O)--, --(CH₂)_(p) C(O)O--,--(CH₂)_(p) OC(O)O--, --O(CH₂)_(p) NR² --, --(CH₂)_(p) NR² C(O)--,--(CH₂)_(p) C(O)NR² --, --(CH₂)NR² C(O)--, --(CH₂)_(p) OC(O)NR² --,--(CH₂)_(p) NR² C(O)NR² -- (in which the R² groups are the same ordifferent), --(CH₂)_(p) O--, --(CH₂)_(p) SO₃ --, and, optionally incombination with B, a valence bond and p is from 1 to 12 and R² ishydrogen or a C₁ -C₄ alkyl group; and wherein the solid blend containsat least 10% by weight of said zwitterionic polymer A.
 25. The method ofclaim 24, in which, in the zwitterionic polymer, X is a zwitterionicgroup in which the anionic moiety is a phosphate group.
 26. The methodof claim 24, in which the cationic moiety of the zwitterionic group islocated at a distant end of the pendant X group from the B group. 27.The method of claim 24, in which the zwitterionic monomer is of theformula ##STR35## in which R is hydrogen, methyl, or ethyl.
 28. Themethod of claim 24, in which R is methyl.
 29. The method of claim 24, inwhich X is selected from groups of formulae (IVB), (IVC), (IVD) and(IVE): ##STR36## where the R⁷ groups are the same or different and eachis hydrogen or a C₁₋₄ alkyl group, and e is from 1 to 4; ##STR37##wherein the R⁸ groups are the same or different and each is hydrogen orC₁₋₄ alkyl group, R^(8a) is hydrogen or a group --C(O)B¹ R^(8b) whereR^(8b) is hydrogen or methyl, B¹ is a valence bond or a straight orbranched alkylene, an oxaalkylene or an oligo-oxaalkylene group, and fis from 1 to 4; and if B is other than valence bond Z is 1 and, if B isa valence bond Z is 0, if X is directly bonded to an oxygen or nitrogenatom and otherwise Z is 1; ##STR38## wherein the R⁹ groups are the sameor different and each is hydrogen or a C₁ -C₄ alkyl group, R^(9a) is ahydrogen or a group --C(O)B² R^(9b) where R^(9b) is hydrogen or methyl,B² is a valence bond or a straight or branched alkylene, an oxaalkyleneor an oligo-oxaalkylene group, and g is from 1 to 4; and if B is otherthan a valence bond Z is 1 and if B is a valence bond Z is 0 if X isdirectly bonded to an oxygen or nitrogen atom and, otherwise Z is 1; and##STR39## wherein the R¹⁰ groups are the same or different and each ishydrogen or a C₁₋₄ alkyl group, R^(10a) is hydrogen or a group --C(O)B³R^(10b) where R^(10b) is hydrogen or methyl, B³ is a valence bond or astraight or branched alkylene, an oxaalkylene or an oligo-oxaalkylenegroup, and h is from 1 to 4; andif B is other than a valence bond Z is 1and if B is a valence bond Z is 0 if X is directly bonded to the oxygenor nitrogen and otherwise Z is
 1. 30. The method of claim 24, in which Xis a group of the formula IVB in which R⁷ groups are all the same andare all methyl.
 31. The method of claim 24, in which the zwitterionicpolymer is formed from monomers including a comonomer of the formula IX

    Y.sup.1 Q.sup.1                                            (IX)

where Y¹ is an ethylenically unsaturated polymerisable group selectedfrom ##STR40## where R¹⁹ is hydrogen or a C₁ -C₄ alkyl group K² isselected from the group consisting of: --(CH₂)_(q) OC(O)--, --(CH₂)_(q)C(O)O--, --(CH₂)OC(O)O--, --(CH₂)NR²⁰ --, --(CH₂)_(q) NR²⁰ C(O)--,--(CH₂)_(q) C(O)NR²⁰ --, --(CH₂)_(q) NR²⁰ C(O)O--, --(CH₂)_(q)OC(O)NR²⁰, --(CH₂)_(q) NR²⁰ C(O)NR²⁰ -- (in which the R²⁰ groups are thesame or different), --(CH₂)_(q) O--, --(CH₂)_(q) O--, --(CH₂)_(q) SO₃--, and a valence bond and q is from 1 to 12 and R²⁰ is hydrogen or a C₁-C₄ alkyl group; and Q¹ is a reactive group capable of reacting toprovide crosslinking within the polymer having desirable physical and/ormechanical properties or to the zwitterionic polymer and/or providing areactive group on the surface of the blend.
 32. The method of claim 24in which the comonomer is a compound of formula ##STR41## wherein: Q² ishydrogen, --OH or a group of the formula:

    --T--B.sup.7 --Q.sup.3                                     (X)

where T is --O--, or --NR²¹ -- where R²¹ is hydrogen, C₁ C₄ alkyl or agroup --B⁷ --Q³ ; wherein B⁷ is a valence bond or a straight or branchedalkylene, an oxaalkylene or an oligo-oxaalkylene chain; and Q³ is areactive group selected from the group consisting of:i) an aldehydegroup, ii) silane and siloxane groups containing one or more reactivesubstituents selected from the group consisting of a halogen or analkoxy containing from 1 to 4 carbon atoms, iii) a hydroxyl group, iv)an amino group, v) a carboxyl group, vi) an epoxy group, vii) --CHOHCH₂Hal, in which Hal is a halogen atom, viii) a succinimido group, ix)sulphonic acid ester groups, x) an imidazole carbonyl-amino group andxi) optionally substituted triazine groups.
 33. The method of claim 24in which the liquid blend is coated onto a solid substrate before theliquid vehicle is evaporated, whereby a coating of the solid blend isformed on the substrate,and further comprising a step of evaporating theliquid.
 34. A method of improving the biocompatibility of a polymer,comprising the steps of:(1) providing a polymer having desirablemechanical and/or physical properties in solution or dispersion in aliquid vehicle to provide a liquid polymer composition; (2) dispersingor dissolving into the liquid polymer composition a zwitterionic polymerA bearing zwitterionic pendent groups to produce a liquid blendedcomposition; optionally in addition dispersing or dissolving into thesaid liquid polymer composition or into said liquid blended compositionat least one additive selected from the group consisting ofplasticisers, fillers, colourants, UV absorbers, antioxidants andpreservatives, said additives being biocompatible; in which thezwitterionic polymer is formed from radical polymerisable monomersincluding at least 5 mole % zwitterionic monomer of formula II

    CH.sub.2═ C(R)C(O)ABX                                  II

wherein B is a straight or branched alkylene, an oxaalkylene or anoligo-oxaalkylene chain optionally containing one or more fluorine atomsup to and including perfluorinated chains; X is a Zwitterionic group,##STR42## in which e is 1 to 4 and each R⁷ is H or C₁₋₄ -alkyl A is--O-- or --NR¹ wherein R¹ is a hydrogen or a C₁ -C₄ alkyl group or R is--B--X where B and X are as defined above; and wherein the liquidcomposition contains at least 10% by weight based on total solids ofpolymer A and up to 90% polymer B.